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Right to Trial & FDA Upgrade Act

Act to modernize medical research and treatment access through an open-source FDA.gov v2, giving patients the right to participate in trials.

Author

Affiliation

Mike P. Sinn

Institute for Accelerated Medicine

Keywords

right-to-trial, fda-upgrade, clinical-trials, drug-development, healthcare-reform, regulatory, patient-rights, open-data, decentralized-trials, fda-v2

Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled,

1 TITLE I: SHORT TITLE; PURPOSE; FINDINGS; DEFINITIONS

1.1 SEC. 101. SHORT TITLE

This Act may be cited as the “Right‑to‑Trial and FDA Upgrade Act.”

1.2 SEC. 102. PURPOSE

The purpose of this Act is to radically accelerate medical progress by:

1. Establishing a right for all patients to participate in decentralized clinical trials for any condition.
2. Creating a zero-knowledge, decentralized global protocol to function as a public utility that dramatically reduces the cost and time of pragmatic clinical trials.
3. Enabling this protocol to aggregate private, individual, time-series health data and publish the results of causal inference analyses that show the change from baseline for any measured outcome after any intervention, tailored to the multiomic cohort most similar to an individual, while maintaining perfect participant anonymity.
4. Providing the open, interoperable infrastructure upon which existing and future clinical trial platforms, electronic health record systems, and other health technologies can integrate and build, transforming the system from a series of disconnected data silos into a unified learning health ecosystem.

How to connect every hospital’s spreadsheet to every other hospital’s spreadsheet without anyone knowing whose liver is whose.

1.3 SEC. 103. FINDINGS

Congress finds the following:

1. New, effective treatments take an average of 17 years to transition from scientific discovery to clinical practice, a delay during which millions of patients suffer without access to potential cures.
2. The current clinical trial paradigm is profoundly inefficient and exclusionary.
   1. Median per‑patient cost for a phase‑3 drug trial in 2024 exceeded $41K[2], inflating drug prices and limiting R‑&‑D on unpatentable therapies.
   2. Up to 86.1 percent of patients are excluded from participating in pivotal trials, limiting the generalizability of findings to real-world patient populations.
   3. The failure to publish negative results leads to redundant research, while rigid trial designs that cannot adapt to incoming data stifle innovation.
   4. The short duration of most trials results in a critical lack of data on the long-term safety and efficacy of an intervention.
3. As a consequence of these systemic failures, an estimated 95 percent of rare diseases lack a single FDA-approved treatment, and effective therapies for common conditions remain undiscovered or inaccessible.
4. The U.K. RECOVERY pragmatic trial enrolled 49,000 patients in 100 days at roughly $500[3], demonstrating that a decentralized, adaptive model can reduce the non-biologic operational costs of clinical research by over 90 percent through automation of data management, monitoring, and administrative functions.
5. The strategic application of artificial intelligence in healthcare has the potential to yield substantial economic benefits, with studies indicating that AI could reduce national healthcare spending by 5 to 10 percent annually by optimizing diagnostics, personalizing treatments, and improving the efficiency of health-related research and development.
6. Publicly financed, algorithm-targeted discounts on patient-borne trial participation costs, aimed at maximizing quality‑adjusted life‑years (QALYs) per federal dollar, can enhance access to trials, with patients covering the net costs of their participation. Funding for these subsidies can be sourced through innovative mechanisms like a decentralized institutes of health (DIH), a global treasury that raises capital by issuing bonds and is repaid by nations participating in a global health treaty.
7. The establishment of a global health data protocol, analogous to the foundational protocols of the internet, is necessary to securely connect disparate data silos and accelerate medical research worldwide. The FDA.gov v2 Decentralized Health Protocol is the United States’ initial contribution to this protocol, a public utility providing the secure, open-source backend for a new generation of health innovation. It creates a global public good by enabling research on all promising therapies, especially those without commercial potential that are underserved by private-sector research.
8. A transparent, open-access reference implementation for trial design, recruitment, data submission, and cost disclosure, as envisioned by the FDA.gov v2 Decentralized Health Protocol, creates a competitive environment among trial sponsors, pushing them to adopt cost-efficient methods and transparent pricing for trial operations.
9. Modernizing FDA regulation to embrace real‑world evidence, remote monitoring, and validated non‑animal test methods accelerates safe cures.
10. The Protocol serves not only the FDA but as shared, open-source public infrastructure for all federal, state, and international health authorities, creating a globally harmonized ecosystem for evidence generation and public health.
11. This Act affirms the fundamental right of every person to access and participate in scientific research relevant to their health. By empowering individuals as both participants and trial creators, the United States can transform its regulatory infrastructure into a global public good, accelerating medical progress for all.
12. The ultimate objective of the Protocol is to evolve into a fully decentralized and autonomous global protocol that is not reliant on the continued stewardship of any single government, corporate entity, or administrative body. The principle of progressive decentralization shall guide its development, ensuring that all governance and operational functions are systematically automated or migrated to secure, on-chain, community-ratified processes, thereby creating a resilient and permanently neutral public utility.

Old trials: slow, expensive, rigid. New trials: fast, cheap, flexible. You’ve been doing this the hard way for decades.

1.4 SEC. 104. DEFINITIONS

In this Act:

1. Secretary means the Secretary of Health and Human Services.
2. FDA means the Food and Drug Administration.
3. NIH means the National Institutes of Health.
4. Pragmatic decentralized trial means a clinical study integrated into routine care, allowing remote or local data capture, minimal exclusions, and broad patient demographics.
5. QALY means a quality‑adjusted life‑year, one year of life in perfect health.
6. FDA.gov v2 Decentralized Health Protocol (the “Protocol”) means the zero-knowledge, decentralized global health protocol initiated by the United States. Its primary function is to serve as a secure, open-source public utility that allows for the aggregation of private, individual, time-series health data. The Protocol is designed to perform and publish causal inference analyses on this aggregated data, showing the change from baseline for any measured outcome after any intervention for the multiomic cohort most similar to a given individual, while preserving the anonymity of all data contributors through cryptographic methods. It is intended to function as a Backend-as-a-Service (BaaS) with which existing and future health platforms (EHRs, clinical trial systems, etc.) can integrate, and is intended for eventual governance by a global, decentralized, on-chain community.
7. Trial Creator means any individual, institution, or entity that designs, initiates, and manages a trial using the Protocol’s reference implementation.
   2. State Laws. No State or political subdivision may regulate the practice of tele‑medicine, pharmacy licensure, or shipment of investigational products in a manner that prevents implementation of this Act. Specifically, a licensed prescriber participating under an FDA‑approved protocol shall be deemed licensed in all States for the limited purpose of providing investigational treatment under this Act, and pharmacies dispensing or shipping such products pursuant to the blockchain supply‑chain ledger are exempt from conflicting State prohibitions.
   3. DSCSA Alignment. All investigational shipments must utilize the protocol’s ledger to satisfy DSCSA traceability.
   4. Shared Public Health Infrastructure. The Protocol shall be designed and maintained as extensible infrastructure available for use by all federal, state, and international health agencies. The Secretary shall establish a process to facilitate the adoption of the Protocol by other agencies for their own regulatory, research, and public health surveillance purposes, thereby creating a shared, globally harmonized ecosystem for evidence generation.

Your DNA and medical records flow through privacy-preserving internet pipes to the FDA and the WHO. Nobody sees your name, everyone sees the patterns.

2 TITLE II: FDA Upgrade AND CLINICAL‑TRIAL INNOVATION

2.1 SEC. 201. ACCELERATED ADOPTION OF ALTERNATIVE PRECLINICAL TEST METHODS

1. Rulemaking. Not later than 180 days after enactment, the Secretary, acting through the Commissioner of Food and Drugs, shall issue final regulations amending 21 CFR Parts 312 and 600 to permit non‑animal New‑Approach Methodologies (NAMs), including organ‑on‑chip systems, validated in‑silico toxicology, and high‑throughput cell assays, as acceptable primary evidence of safety where scientifically justified.
2. Qualification pathway. The regulations shall establish a transparent qualification pathway; once a NAM is qualified for a defined context of use, FDA reviewers shall accept data from that method without requiring parallel animal studies.
3. Annual report. The Commissioner shall publish an annual public report enumerating qualified NAMs, sponsor submissions using NAMs, and areas still requiring animal use with timelines to develop alternatives.

How to make the FDA accept computer models and lab-grown cells instead of killing mice. It’s a multi-step bureaucratic process, naturally.

2.2 SEC. 202. GUIDANCE ON DECENTRALISED, ADAPTIVE, AND REAL‑WORLD‑EVIDENCE TRIALS

1. Decentralised Trials Guidance. Within 1 year the Secretary shall issue final guidance recognising remote visits, tele‑investigator oversight, direct‑to‑patient IMP shipment, and e‑consent, as compliant with 21 CFR Parts 50, 54, and 312.
2. Adaptive Designs. Guidance shall allow response‑adaptive randomisation, Bayesian interim analyses, seamless phase 2/3 designs, and platform/master‑protocol structures, provided pre‑specified statistical control of type‑I error.
3. Real‑World Evidence. Within 18 months the Secretary shall publish a framework specifying how real‑world data (EHRs, claims, device feeds) integrated via the FDA v2 Protocol may support new indications, post‑marketing commitments, or safety label changes.
4. Training. FDA shall establish continuing‑education modules to train reviewers in decentralized‑trial oversight, Bayesian statistics, and RWE analytics.

Four ways to make drug trials faster: run them remotely, change them mid-study, use real patient data, and teach the regulators how.

2.3 SEC. 203. PATIENT‑FOCUSED DRUG DEVELOPMENT AND GLOBAL COLLABORATION

1. Patient Experience Integration. FDA shall revise Patient‑Focused Drug Development guidance to require that every pivotal trial protocol include at least one patient‑reported outcome or patient‑preference study relevant to benefit–risk assessment.
2. Global Work‑sharing. The Secretary may enter into work‑sharing arrangements with peer regulators (EMA, PMDA, Health Canada) for concurrent review of applications utilising FDA v2 Protocol data.
3. Data Standards Convergence. The Secretary shall align FDA data standards with HL7 FHIR Release 5, CDISC SDTM v4, and SNOMED‑CT 2025 edition to ensure cross‑border data utility.

Ask patients how they feel, get all countries to review drugs at once, and make everyone use the same spreadsheet format. Simple.

2.4 SEC. 204. FDA.gov v2 DECENTRALIZED HEALTH PROTOCOL AND REFERENCE IMPLEMENTATION

1. Launch & Hosting. Within 12 months after enactment, the Secretary shall deploy an open-source, cloud-native FDA.gov v2 Decentralized Health Protocol, which shall include the FDA.gov Public Portal hosted on the fda.gov domain. All source code shall be mirrored in real-time to a public repository (e.g., github.com/fda/fda-v2).
2. Mandatory Open‑Source Licence. All code shall be released under the GNU General Public License v3.0. Any proprietary dependency shall be replaced or dual‑licensed within 24 months.
3. Trial Creator Workspace Functions. The FDA.gov Public Portal shall provide:

1. E‑Protocol Builder with templates and automated compliance validation (21 CFR Parts 312/812, ISO 14155) that lets any Trial Creator, regardless of prior regulatory expertise, design and launch a study.
2. Liability‑Insurance Exchange for real‑time per‑subject quotes; selections auto‑populate FDA Form 1572.
3. Trial Cost, Discount, and Deposit Module facilitating: (A) the transparent calculation and disclosure of estimated patient-specific trial participation costs as provided by the trial sponsor; (B) the application of any applicable NIH-funded participation discounts (pursuant to SEC. 303); (C) the management of the net financial contribution required from the participant (as per SEC. 304(b)); and (D) the collection, holding, and refund of a patient data provision deposit (as per SEC. 304). All cost components, applicable discounts, the final net cost to the participant, and details of the data provision deposit shall be clearly itemized and presented to the participant during the e-consent process (as per SEC. 302(b) and SEC. 304).
4. Blockchain Supply‑Chain Ledger[9] interoperable with DSCSA (§ 360eee‑3) to capture temperature, custody, delivery.
5. Live Analytics Dashboards for enrolment, compliance, blinded efficacy; regulators & IRBs get read‑only oversight.

4. Core Protocol Services and Public Reference Portal. The Protocol’s primary function is to provide core backend services accessible via its open API. To ensure baseline access for all citizens and to serve as a model for third-party developers, the Secretary shall host the public-facing FDA.gov Public Portal as part of the reference implementation. This framework shall:

1. Provide a Reference Health Analysis Tool. The portal lets users connect their data to a secure reference agent that integrates and analyzes their health information to generate a ranked list of treatments & trials, presented alongside standardized “Outcome Labels.”
2. Enable User-Initiated Data Contribution. The Protocol shall provide standardized tools (including APIs and SDKs) that let individuals securely contribute their health data from diverse sources. All data sharing shall be explicitly initiated and authorized by the user.
3. Provide reference interfaces for single‑session e‑screening, Part 11 e‑consent, and instant randomisation for matched trials through the portal.
4. Coordinate direct‑to‑patient or local‑pharmacy IMP dispatch with ledger verification.
5. Capture outcomes via mobile app, SMS/IVR, FHIR push, and IoT feeds; data loop into evidence rankings which are recomputed nightly. The source code, feature weights, and a reproducible computational notebook for each annual release of the QALY‑ranking algorithm shall be posted in the public repository within 30 days of model deployment.
6. Contribute to and draw from a Publicly Accessible Knowledge Base (dubbed “Clinipedia”) of all quantified food and drug effects, continuously updated with new data and analysis from the Protocol. This knowledge base, including all underlying data, analytical models, and evidence rankings, shall be made easily searchable and accessible to all, serving as a global public good.

5. The Protocol’s Open API. The Protocol shall function as a Backend-as-a-Service (BaaS) for the national health technology ecosystem. Its primary deliverable is the secure, versioned, and documented open API. All de‑identified data shall be exposed through this RESTful API that is HL7 FHIR‑R5 compliant and meets 42 U.S.C. § 300jj‑52. The reference implementation is explicitly intended not to compete with consumer-facing applications but to provide the secure, interoperable rails upon which a competitive ecosystem of third-party tools and services can be built.
6. Continuous Integration/Continuous Deployment (CI/CD). The Secretary shall maintain automated unit‑test, security‑scan, and code‑quality pipelines that must pass before any code merge. CI results shall be publicly viewable and the Protocol’s reference implementation shall maintain compliance with FedRAMP‑Moderate[6] and NIST SP 800‑218 DevSecOps guidelines; the System Security Plan and Authority‑to‑Operate letter shall be posted in redacted form.
7. AI-Augmented Governance & Pull‑Request Acceptance.

1. AI-Assisted Review. All pull requests (PRs) submitted to the public repository shall undergo an automated, comprehensive review by one or more designated AI Governance and Security Review systems. These systems shall be open-source and trained to perform deep code analysis, identify potential vulnerabilities, assess compliance with architectural standards, and model the risk of economic exploits.
2. Risk-Based Triage. The AI Reviewer shall assign each PR a risk score (e.g., “Low,” “Medium,” “High,” “Critical”). This score determines the review and merge process:

1. Low-Risk PRs: Shall be merged automatically within 72 hours if they pass all CI tests, unless a TSC member manually flags it for review.
2. Medium-Risk PRs: Shall be automatically paused and require an explicit simple majority approval vote from the TSC for merger.
3. High-Risk or Critical-Risk PRs: Shall be automatically rejected and may not be merged without a two-thirds supermajority vote from the TSC to override the AI’s finding, accompanied by a published justification.

3. Technical Steering Committee (TSC). A nine‑member TSC is hereby established to oversee the repository, adjudicate flagged PRs, and manage the AI Governance Reviewers. The TSC is mandated to continuously pursue the automation and decentralization of its own functions, with the long-term goal of migrating governance decisions to a secure, on-chain, community-ratified process. To ensure this transition, the authority of the TSC as constituted herein shall sunset no later than 7 years after the date of enactment of this Act, or upon a determination by the Secretary that a secure and viable on-chain governance model is operational, whichever is earlier. The final act of the TSC shall be to ratify the migration to the successor governance protocol. Composition: 2 FDA officials, 1 NIH representative, 1 representative from a peer international regulator (e.g., EMA, PMDA), 1 patient‑advocacy representative, 1 open‑source AI/ML security expert elected by contributors, 1 biostatistician, 1 cyber‑security expert, and 1 industry sponsor representative. The Secretary shall pursue agreements to add representatives from at least two other international health authorities or bodies within 24 months.
4. Appeal and Manual Override. Any contributor may appeal an AI rejection or TSC decision to the FDA Chief Scientist, who must respond within 30 days. The TSC retains the authority to manually re-classify any PR with a two-thirds vote.
5. Democratic Renewal. The community-elected AI/ML security expert and patient-advocate seats are subject to annual election by contributors (defined as those with ≥5 merged PRs in the preceding year) using ranked‑choice voting via a transparent, verifiable online ballot.

8. Rulemaking & PRA Fast‑Track. Within 180 days the Secretary shall issue interim final rules specifying technical standards for each module, standards for the content, format, and regular updating of Outcome Labels mandated under subsection (d)(1) of this section, codifying the TSC charter, and invoking 44 U.S.C. § 3507(h) such that any Information‑Collection Request[5] tied to the FDA v2 Protocol obtains OMB clearance within 60 days. Sponsors or investigators that fail to comply with these rules may be suspended under 21 U.S.C. § 331(f).

The FDA, but running on GitHub with AI code review and a blockchain receipt system. Democracy meets software development.

1. Public‑Bounty & Zero‑Knowledge Ledger. The Secretary shall operate a continuous public bounty program, funded under § 402(a), to reward external contributors for merged pull‑requests, vulnerability disclosures, and feature enhancements. The AI Governance and Security Reviewer shall be used to automatically verify vulnerability submissions, score their severity, and recommend payment amounts to expedite the bounty process. Bounties shall be posted openly as issues in the public repository with dollar amounts and paid within 30 days of merge. Furthermore, all patient‑level data aggregated and analyzed by the Protocol shall be represented as zero‑knowledge proofs (e.g., zk‑SNARK commitments) and stored via content‑addressable storage, permitting any nation‑state or regional authority to run an independent mirror node and verify ledger integrity without accessing protected health information.

10. Metrics & Transparency. Annual public report: protocol uptime, median time‑to‑trial launch, pull‑request merge rate, unresolved PR backlog, bounty payouts, penetration‑test findings, insurance‑premium benchmarks, and user‑satisfaction scores. The Secretary shall commission an independent penetration test every fiscal year and publish an executive summary of findings.

11. Protocol Intelligence and Automation. The Protocol shall leverage artificial intelligence and machine learning capabilities to enhance its functionalities, including but not limited to: (1) assisting sponsors with automated protocol validation checks during e-protocol building; (2) improving the precision of matching patients to suitable trials based on their comprehensive health data; (3) augmenting the analysis of aggregated, de-identified data for early safety signal detection and pharmacovigilance; (4) powering the AI Governance and Security Reviewer for automated code review, vulnerability detection, and pull-request adjudication as specified in subsection (g); and (5) supporting regulatory staff with tools for efficient data review where appropriate. All such AI/ML systems shall be developed with robust validation, transparency in function, and operate under human oversight, particularly for critical decision support.

12. Global Accessibility. To facilitate global participation and data collection, the FDA.gov Public Portal’s user interfaces for patients and trial creators shall be made accessible in multiple languages.

13. Interoperability with National Health Data Systems. The Protocol shall be designed to complement and enhance existing government health initiatives. The Secretary shall establish data sharing and interoperability frameworks to connect the Protocol with key national health programs, including but not limited to: the FDA’s Sentinel Initiative and Global Substance Registry System (GSRS); the National Institutes of Health’s All of Us Research Program; the National Health and Nutrition Examination Survey (NHANES); and the Centers for Disease Control and Prevention’s public health surveillance systems. This integration shall leverage the Protocol’s AI capabilities to analyze data across systems, enhancing national safety monitoring, research, and public health response capabilities while adhering to strict privacy-preserving protocols.

2.5 SEC. 205. FDA-X PRIZE

1. Establishment. To accelerate the development of the FDA.gov v2 Protocol, the Secretary is authorized to establish an “FDA-X Prize” competition, with a prize purse to be determined by the Secretary, awarded to the entity that first develops and demonstrates a public portal meeting the core requirements outlined in Section 204 and which demonstrates the capacity to achieve at least an 80X reduction in per-patient trial costs compared to traditional methodologies.

Offer a prize for cutting FDA approval costs by 80X. Somebody wins. Integrate their solution. Government runs a hackathon.

2. Alternative Development Path. The Secretary may use the prize competition as the primary mechanism for developing the protocol. In such a case, the timelines and responsibilities outlined in Section 204(a) shall be adjusted to reflect a successful prize outcome.
3. Integration. If the prize is awarded for a platform that meets a substantial subset of requirements, the Secretary shall ensure its integration with any components developed or procured under Section 204.

3 TITLE III: UNIVERSAL TRIAL ACCESS (RIGHT‑TO‑TRIAL PROGRAM)

3.1 SEC. 301. UNIVERSAL ELIGIBILITY FOR INVESTIGATIONAL INTERVENTIONS

1. Right. Beginning 24 months after enactment, any U.S. resident who requests an investigational intervention shall be guaranteed enrolment, remotely if necessary, in at least one pragmatic, decentralized trial arm evaluating that intervention, subject to the safety-based exclusions specified in subsection (c).

Drug companies can run your trial for profit. If they don’t want you, the government runs a mini-trial in 60 days. Nobody gets excluded.

2. Sponsor Incentive. The Secretary shall award a transferable Priority‑Review Voucher (PRV) under section 524A of the Federal Food, Drug, and Cosmetic Act to any sponsor that, on or before the universal‑enrolment activation date, opens or amends a trial on the FDA.gov Public Portal to accept such patient‑directed enrolment and maintains adequate investigational‑product supply. A PRV is forfeited if the sponsor later restricts patient enrolment without a documented safety or manufacturing constraint.

3. Safety‑Based Exclusions Only. Sponsors or IRBs may exclude an individual patient solely for documented, evidence‑based safety reasons (e.g., a specific contraindication, allergy, or organ‑system risk) or if investigational‑product supply is demonstrably insufficient. Exclusion rationales must be transmitted to the FDA Dashboard within 7 days and are subject to FDA audit.

4. NIH Micro‑Study Fallback. If no sponsor operates an active investigational‑new‑drug application that can accept the patient within 60 days of request, the NIH, using Other Transaction Authority, shall initiate a single‑arm or adaptive micro‑study to provide the intervention under IND and collect outcomes via the Protocol; such micro‑studies qualify for subsidies under § 303.

5. Adaptive Enrolment. Sponsors participating under this section must accept data‑driven lowering of exclusion criteria unless an IRB documents incremental safety risk.

3.2 SEC. 302. PATIENT PROTECTIONS, CONSENT, AND LIABILITY

1. Ethical Oversight. All Right‑to‑Trial protocols shall undergo review by a qualified Institutional Review Board (IRB). To foster innovation and efficiency, the FDA.gov v2 Protocol shall support both review by a single central IRB (per 45 CFR § 46.114[8]) and by qualified Decentralized Ethical Review Boards (DERBs). The Secretary shall, through rulemaking, establish standards for the qualification, operation, and oversight of DERBs on the Protocol.
2. Informed Consent and Comprehension Verification.

1. E-consent via the FDA.gov Public Portal shall clearly disclose, in an accessible format, the investigational nature of the trial, all known and potential risks including their likelihood based on available data (with particular emphasis on the most serious risks), the full details of patient financial responsibilities including the net cost contribution and the refundable data provision deposit (as detailed in SEC. 304), potential benefits, alternative treatments, and all data-sharing terms.
2. To verify genuine understanding of the disclosed information, particularly concerning the most serious risks and their likelihood, successful completion of the e-consent process shall require the patient to pass an automated, interactive comprehension quiz administered through the FDA.gov Public Portal. This quiz shall be based directly on the information disclosed pursuant to paragraph (1) of this subsection.
3. The Secretary, through rulemaking within 12 months of enactment, shall establish standards for the development, content, validation, and administration of such comprehension quizzes, including criteria for successful completion and procedures for patients who do not initially pass. These standards shall ensure quizzes are fair, accessible, and effectively assess understanding of critical information.
4. Execution of the e-consent, following successful completion of the comprehension quiz, constitutes both 45 CFR § 164.508 authorization and, where applicable, a waiver of authorization under § 164.512(i)[11] for research use of protected health information, as approved by the reviewing IRB. A record of successful quiz completion and the signed consent shall be hashed and stored on the blockchain ledger.

3. Safety Monitoring. Sponsors must stream adverse‑event data to the Dashboard within 24 hours; FDA may halt enrolment under 21 CFR § 312.42.
4. Liability Shield. Good‑faith compliance grants immunity from tort claims except for gross negligence or willful misconduct; mirrors Pub. L. 115‑176 § 2(c).

You click buttons until the computer is sure you understand the trial. Your consent lives on a blockchain. Sensors watch for side effects in real time.

3.3 SEC. 303. FAIR ACCESS AND DISCOUNT ALGORITHMS

1. Fund. A revolving Clinical Trial Patient Cost Discount Fund is hereby established within the Treasury, authorized to receive $2 billion for each of fiscal years 2026 through 2030.

Money flows from Treasury through an optimization algorithm to trials while data flows from patients to the FDA. Everyone gets paid, everyone gets informed.

2. Discount Allocation Algorithm. The NIH Director shall develop, publish, and annually recompute a transparent, open-source optimisation model for the allocation of discounts from the Fund. This model shall determine the percentage or amount of discount applicable to patient-borne costs for participation in specific trials available on the FDA v2 Protocol. The primary objectives for discount allocation shall be: (1) maximizing projected quality-adjusted life-years (QALYs) gained per dollar of discount provided; (2) the potential for significant healthcare system cost savings attributable to the research; and (3) the marginal scientific value of the pragmatic clinical trial, including its potential to reduce uncertainty for interventions with limited existing evidence but high potential impact. The algorithm shall dynamically incorporate new evidence on treatment efficacy, safety, and cost-effectiveness generated through the FDA v2 Protocol.

3. Application of Discounts. Upon a patient’s enrolment in a trial via the FDA v2 Protocol, the NIH shall authorize the application of the algorithmically determined discount to the patient’s share of trial participation costs, as itemized by the sponsor and displayed on the FDA.gov Public Portal (per SEC. 204(c)(3) and SEC. 304). The Fund shall cover the discounted portion of such costs. Sponsors shall certify the full, itemized costs of participation and submit all required trial outcome data for continued eligibility to have their trials included in the discount program.

4. Audit. The Comptroller General of the United States shall audit the allocation and application of discounts from the Fund biennially and report findings to Congress. The Secretary may recoup any funds associated with discounts applied to mis-certified costs or for trials not meeting data submission requirements.

3.4 SEC. 304. PATIENT COST CONTRIBUTION FOR TRIAL PARTICIPATION

1. Determination and Disclosure of Participation Costs. Prior to a patient consenting to a trial, the sponsoring entity shall determine and provide to the FDA v2 Decentralized Health Protocol a comprehensive, itemized estimate of all direct costs associated with that specific patient’s anticipated participation in the trial. This shall include, but not be limited to, costs of investigational product, necessary medical procedures, diagnostic tests, monitoring, and data management directly attributable to the research participant. These estimated costs, alongside the NIH-funded discount applicable under SEC. 303, and the final net cost to the patient, shall be transparently displayed to the potential participant via the FDA.gov Public Portal (SEC. 204(c)(3)) and detailed in the e-consent form (SEC. 302(b)). This transparent disclosure of itemized costs on a decentralized framework is intended to encourage competitive and efficient pricing by sponsoring entities.

Sponsors pay for trials. NIH offers discounts. Patients get refunds if sponsors misuse their data. It’s healthcare with a money-back guarantee.

2. Patient Net Cost Contribution. Each participant shall be responsible for contributing the net cost of their trial participation, calculated as the estimated total direct cost of participation (as determined in subsection (a) of this section) minus the NIH-funded discount (as determined and applied under SEC. 303). The FDA.gov Public Portal shall facilitate the management of this net cost contribution.
3. Prohibition on Additional Charges. Sponsors or investigating sites may not bill or charge a participant for any costs related to their trial participation beyond the final net cost contribution calculated and disclosed through the FDA v2 Protocol as per subsections (a) and (b) of this section. Participants shall retain the right to terminate their participation in the trial at any time, subject to standard clinical and ethical procedures; financial obligations will be prorated based on the extent of participation and disclosed costs.
4. Financial Hardship Considerations. The Secretary, in consultation with NIH, may establish guidelines or auxiliary programs to address financial hardship for patients for whom the net cost contribution, even after applicable discounts, remains a significant barrier to accessing trials deemed of high public health value or for conditions with limited alternative treatments. Such guidelines shall not obligate sponsors to cover these costs unless through separate, voluntary programs, but may coordinate with external funding sources, such as those that might be allocated through a decentralized institutes of health (DIH) framework.
5. Refundable Data Provision Deposit.

1. To incentivize the complete and timely submission of all data required by the trial protocol, each participant shall provide a refundable data provision deposit. The amount of such deposit shall be established by the Secretary through rulemaking, considering factors such as trial duration, data complexity, and the need to avoid undue financial burden on participants.
2. The deposit shall be collected by the FDA v2 Protocol’s Trial Cost, Discount, and Deposit Module (as per SEC. 204(c)(3)) at the time of e-consent.
3. The full deposit shall be refunded to the participant via the FDA.gov Public Portal upon certification by the trial sponsor or a designated Platform administrator that the participant has provided all protocol-required data within the specified timeframes.
4. Conditions for partial refund or forfeiture of the deposit due to incomplete or untimely data submission shall be detailed in the e-consent form (SEC. 302(b)) and established by the Secretary through rulemaking. Forfeited deposits may be directed to the Clinical Trial Patient Cost Discount Fund (SEC. 303) or used to offset costs incurred by data remediation efforts.

4 TITLE IV: GENERAL PROVISIONS

4.1 SEC. 401. COORDINATION WITH EXISTING LAW

1. Expanded Access. This Act supplements 21 CFR § 312 Subpart I; data from Right‑to‑Trial may fulfill post‑marketing study obligations.
2. State Laws. No State or political subdivision may regulate the practice of tele‑medicine, pharmacy licensure, or shipment of investigational products in a manner that prevents implementation of this Act. Specifically, a licensed prescriber participating under an FDA‑approved protocol shall be deemed licensed in all States for the limited purpose of providing investigational treatment under this Act, and pharmacies dispensing or shipping such products pursuant to the blockchain supply‑chain ledger are exempt from conflicting State prohibitions.
3. DSCSA Alignment. All investigational shipments must utilize the protocol’s ledger to satisfy DSCSA traceability.
4. Shared Public Health Infrastructure. The Protocol shall be designed and maintained as extensible infrastructure available for use by all federal, state, and international health agencies. The Secretary shall establish a process to facilitate the adoption of the Protocol by other agencies for their own regulatory, research, and public health surveillance purposes, thereby creating a shared, globally harmonized ecosystem for evidence generation.

One blockchain to replace fifty state licensing systems, drug tracking rules, and international health agency paperwork. Efficiency looks like simplification.

4.2 SEC. 402. AUTHORIZATION OF APPROPRIATIONS AND STAGE‑GATED FUNDING

1. FDA Upgrade. $500 million FY 2026‑30, of which no more than 25 percent may be obligated until the FDA.gov Public Portal (1) attains FedRAMP‑Moderate ATO and (2) records at least 1,000 merged pull‑requests under § 204(g). Subsequent 25‑percent tranches unlock upon the Protocol reaching 10,000 users and 10,000 merged pull‑requests, respectively.
2. Subsidy Fund. $2 billion FY 2026‑30, released quarterly upon NIH certification that the subsidy‑allocation algorithm achieved or exceeded its projected QALY gain in the preceding quarter.
3. Regulatory‑Science Grants. $150 million FY 2026‑30.
4. Direct‑Hire Authority. For FY 2026‑30 the Secretary may hire up to 200 technical employees for the framework under 5 U.S.C. § 9803 (critical‑need direct hire).
5. Agile Acquisition Pilot. All contracts for the framework are designated “modular IT acquisitions” under FITARA; FAR Part 15 documentation requirements are waived in favour of the US Digital Service Playbook[10] incremental‑delivery model.** $150 million FY 2026‑30.

4.3 SEC. 403. IMPLEMENTATION TIMELINE

• 180 days: Interim rules; beta e‑protocol builder; transparency website live.
• 24 months: FDA v2 Platform MVP; insurance exchange; blockchain ledger operational.
• 36 months: Universal enrolment guarantee active; subsidies flowing.
• 48 months: First GAO report to Congress.

Year one: make temporary rules. Years two through four: make them permanent while the Government Accountability Office watches and takes notes.

4.4 SEC. 404. STRATEGY FOR GLOBAL GOVERNANCE AND DECENTRALIZATION

1. Objective. The Secretary, in coordination with the Secretary of State, shall develop and execute a strategy to transition the governance of the Protocol from the United States government to an independent, international multi-stakeholder body.
2. Report to Congress. Within 18 months of enactment, the Secretary shall submit a report to Congress outlining this strategy, including: (1) proposed frameworks for a new international governance body; (2) a timeline for transitioning technical and administrative oversight; and (3) a plan for ensuring the long-term sustainability and neutrality of the protocol, including research into and pathways toward cryptographically-secured, on-chain governance models that reduce reliance on a central administrative body.
3. Continued Support. The United States shall continue to provide technical and financial support for the Protocol during a transition period of no less than 5 years after an international governance body is established.

The U.S. runs it first, then gives it to an international committee, then gives it to a blockchain. Centralization fades like training wheels.

4.5 SEC. 405. SEVERABILITY

If any provision of this Act is held invalid, the remainder shall remain in effect.

4.6 SEC. 406. TRANSPARENCY IN REGULATORY ACTIONS LIMITING TREATMENT ACCESS

1. Public Justification Reports Required. For any regulatory action taken by the Secretary that denies, restricts, or withdraws patient access to any potential treatment, the Secretary shall, within 60 days of such action, publish a comprehensive report. This report shall be publicly available on the FDA.gov Public Portal.

Before the FDA makes a rule, AI models the consequences, the public comments, and independent auditors check the work. Regulation gets peer review.

2. Content of Report. Such report shall include, at a minimum: (1) a detailed summary of the scientific evidence regarding the treatment’s benefits and risks considered by the Secretary, including available clinical endpoint data; (2) the specific rationale for the regulatory action, including any statutory obligations influencing the decision; (3) an analysis of the anticipated impact of the action on patient populations, including consideration of available alternatives, unmet medical needs, and a summary of available information on potential health economic consequences, including, where feasible and appropriate, a qualitative or quantitative assessment of costs and benefits; provided that, upon certification by the Secretary that the capabilities developed under subsection (d) are sufficiently mature, such assessment shall include a quantitative health and economic modeling simulation as detailed therein; (4) an explanation of why less restrictive regulatory measures, if applicable, were deemed insufficient; and (5) any dissenting opinions from within the review team or advisory committees, if applicable.

3. Retention of Authority. Nothing in this section shall be construed to limit the Secretary’s authority to take necessary regulatory action to protect public health, including in emergency situations. In such cases, the report shall be published as soon as practicable following the action.

4. Development of Advanced Modeling Capabilities for Treatment Access Reports. The Secretary, in consultation with the Director of the NIH and the Director of the Agency for Healthcare Research Quality (AHRQ), shall, within 2 years of enactment, establish and ensure the operational maturity of robust capabilities for conducting the quantitative health and economic modeling simulations necessary to fulfill the reporting requirements under subsection (b) of this section. This shall include utilizing data from the FDA v2 Protocol, defining appropriate resource allocation from the NIH and other sources, and developing automated AI-driven workflows where feasible.

5. Comprehensive Impact Analysis of All General FDA Rules, Guidance, and Policies.

1. Mandate for Analysis: To ensure all Food and Drug Administration (FDA) activities are demonstrably in the public interest and to quantify their effects on public health and the economy, the Secretary shall ensure that every proposed and existing FDA regulation (as defined in 21 C.F.R. Part 10), formal guidance document, and other generally applicable policy statement (hereinafter collectively referred to as “regulatory instruments”) undergoes a comprehensive, quantitative health and economic impact analysis as specified in this subsection.
2. Prospective Analysis of New Regulatory Instruments: Except as provided in subsection (c) of this section for emergency actions, no new FDA regulatory instrument shall be finalized, issued, or take effect until a comprehensive impact analysis, meeting the requirements of paragraph (e)(4) of this subsection, has been completed, made public on the FDA.gov Public Portal for a period of no less than 60 days for public comment, and its findings explicitly considered and addressed by the Secretary in the final issuance. For emergency actions, the analysis shall be completed and published within 90 days of the instrument taking effect.
3. Retrospective Analysis and Review of Existing Regulatory Instruments: The Secretary shall, within 1 year of enactment, establish and publish a prioritized schedule for the systematic review and comprehensive impact analysis of all significant existing FDA regulatory instruments. This schedule shall ensure that all such instruments are analyzed within 7 years of enactment. All analyses conducted under this subsection shall be updated at least every 5 years, or more frequently if significant new evidence or modeling capabilities emerge.
4. Standards for Comprehensive Impact Analysis: Each analysis conducted under this subsection (e) shall:

1. Be supported by dedicated resources, including a prespecified minimum percentage of the annual budget of the National Institutes of Health, to ensure its capacity, independence, and timeliness.
2. Be based on a systematic review of all available global evidence, incorporate rigorous quantitative uncertainty characterization, and calculate projected individual and population-level health outcomes (including, but not limited to, quality-adjusted life-years (QALYs) gained or lost) and economic consequences (including, but not limited to, Incremental Cost-Effectiveness Ratios (ICERs) and direct and indirect costs to patients, the healthcare system, and society). Sensitivity analyses shall be conducted for all key assumptions.
3. Be developed and executed primarily by advanced autonomous AI systems to ensure speed, consistency, and comprehensiveness. The role of human personnel shall be focused on oversight, final review, and the adjudication of complex edge cases flagged by the AI. All software, algorithms, data inputs, and models developed or utilized for these analyses shall be released under an open-source licence approved by the Open Source Initiative, published on the FDA.gov Public Portal, and subject to mechanisms that facilitate public inspection, contribution, and collaborative improvement, consistent with the AI-augmented governance principles outlined in SEC. 204(g);
4. Be made publicly available in its entirety, including all underlying data, assumptions, and models, on the FDA.gov Public Portal in a user-friendly and accessible format.

5. Independent Oversight and Audit: An independent office within the Department of Health and Human Services, separate from the Food and Drug Administration, shall be established or designated to oversee the methodologies, execution, and audit of analyses conducted under this subsection (e) to ensure objectivity and scientific integrity.
6. Public Petition for Analysis: Any member of the public may petition the Secretary for a comprehensive impact analysis of any specific FDA regulatory instrument not yet analyzed or not recently updated. The Secretary shall respond to such petitions within 120 days, either by initiating the analysis or by publishing a detailed justification for denial, which shall itself be subject to review by the independent office established under paragraph (e)(5).
7. Consideration in FDA Actions and Legal Standing: The FDA shall be required to explicitly consider and publicly respond to the findings of these impact analyses in all subsequent rulemaking, policy development, enforcement activities, and in the review of existing regulatory instruments. Failure to conduct or appropriately consider such analyses as mandated herein shall be grounds for legal challenge to the validity or application of the regulatory instrument.

4.7 REFERENCES

[1] ClinicalTrials.gov FY 2024 Annual Report, Table 4 (trial enrollment). [2] Moore, T. J., Zhang, H., Anderson, G., & Alexander, G. C. (2018). Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2016. JAMA Internal Medicine, 178(11), 1451–1457. [3] See Decentralized Pragmatic Trials (RECOVERY) analysis, citing UKRI, Manhattan Institute, and others. [4] openFDA GitHub Repository, https://github.com/FDA. [5] 44 U.S.C. § 3507(h) fast‑track provision; Administrative Conference PRA Study (2012). [6] FedRAMP FAQ, ‘Understanding Baselines & Impact Levels’ (2024). [7] 42 CFR § 1001.952(bb) (value‑based safe‑harbour). [8] 45 CFR § 46.114, NIH Single‑IRB Policy (updated 2023). [9] FDA DSCSA Pilot Project Program – Final Report (2024). [10] U.S. Digital Service, Digital Service Playbook (2025). [11] 45 CFR § 164.512(i)(1) (HIPAA research waiver).

4.7.1 End of Act.

1.

NIH Common Fund. NIH pragmatic trials: Minimal funding despite 30x cost advantage. NIH Common Fund: HCS Research Collaboratory https://commonfund.nih.gov/hcscollaboratory (2025)

The NIH Pragmatic Trials Collaboratory funds trials at $500K for planning phase, $1M/year for implementation-a tiny fraction of NIH’s budget. The ADAPTABLE trial cost $14 million for 15,076 patients (= $929/patient) versus $420 million for a similar traditional RCT (30x cheaper), yet pragmatic trials remain severely underfunded. PCORnet infrastructure enables real-world trials embedded in healthcare systems, but receives minimal support compared to basic research funding. Additional sources: https://commonfund.nih.gov/hcscollaboratory | https://pcornet.org/wp-content/uploads/2025/08/ADAPTABLE_Lay_Summary_21JUL2025.pdf | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604499/

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2.

NIH. Antidepressant clinical trial exclusion rates. Zimmerman et al. https://pubmed.ncbi.nlm.nih.gov/26276679/ (2015)

Mean exclusion rate: 86.1% across 158 antidepressant efficacy trials (range: 44.4% to 99.8%) More than 82% of real-world depression patients would be ineligible for antidepressant registration trials Exclusion rates increased over time: 91.4% (2010-2014) vs. 83.8% (1995-2009) Most common exclusions: comorbid psychiatric disorders, age restrictions, insufficient depression severity, medical conditions Emergency psychiatry patients: only 3.3% eligible (96.7% excluded) when applying 9 common exclusion criteria Only a minority of depressed patients seen in clinical practice are likely to be eligible for most AETs Note: Generalizability of antidepressant trials has decreased over time, with increasingly stringent exclusion criteria eliminating patients who would actually use the drugs in clinical practice Additional sources: https://pubmed.ncbi.nlm.nih.gov/26276679/ | https://pubmed.ncbi.nlm.nih.gov/26164052/ | https://www.wolterskluwer.com/en/news/antidepressant-trials-exclude-most-real-world-patients-with-depression

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3.

CNBC. Warren buffett’s career average investment return. CNBC https://www.cnbc.com/2025/05/05/warren-buffetts-return-tally-after-60-years-5502284percent.html (2025)

Berkshire’s compounded annual return from 1965 through 2024 was 19.9%, nearly double the 10.4% recorded by the S&P 500. Berkshire shares skyrocketed 5,502,284% compared to the S&P 500’s 39,054% rise during that period. Additional sources: https://www.cnbc.com/2025/05/05/warren-buffetts-return-tally-after-60-years-5502284percent.html | https://www.slickcharts.com/berkshire-hathaway/returns

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4.

World Health Organization. WHO global health estimates 2024. World Health Organization https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates (2024)

Comprehensive mortality and morbidity data by cause, age, sex, country, and year Global mortality:  55-60 million deaths annually Lives saved by modern medicine (vaccines, cardiovascular drugs, oncology):  12M annually (conservative aggregate) Leading causes of death: Cardiovascular disease (17.9M), Cancer (10.3M), Respiratory disease (4.0M) Note: Baseline data for regulatory mortality analysis. Conservative estimate of pharmaceutical impact based on WHO immunization data (4.5M/year from vaccines) + cardiovascular interventions (3.3M/year) + oncology (1.5M/year) + other therapies. Additional sources: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates

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5.

GiveWell. GiveWell cost per life saved for top charities (2024). GiveWell: Top Charities https://www.givewell.org/charities/top-charities

General range: $3,000-$5,500 per life saved (GiveWell top charities) Helen Keller International (Vitamin A): $3,500 average (2022-2024); varies $1,000-$8,500 by country Against Malaria Foundation: $5,500 per life saved New Incentives (vaccination incentives): $4,500 per life saved Malaria Consortium (seasonal malaria chemoprevention):  $3,500 per life saved VAS program details:  $2 to provide vitamin A supplements to child for one year Note: Figures accurate for 2024. Helen Keller VAS program has wide country variation ($1K-$8.5K) but $3,500 is accurate average. Among most cost-effective interventions globally Additional sources: https://www.givewell.org/charities/top-charities | https://www.givewell.org/charities/helen-keller-international | https://ourworldindata.org/cost-effectiveness

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6.

AARP. Unpaid caregiver hours and economic value. AARP 2023 https://www.aarp.org/caregiving/financial-legal/info-2023/unpaid-caregivers-provide-billions-in-care.html (2023)

Average family caregiver: 25-26 hours per week (100-104 hours per month) 38 million caregivers providing 36 billion hours of care annually Economic value: $16.59 per hour = $600 billion total annual value (2021) 28% of people provided eldercare on a given day, averaging 3.9 hours when providing care Caregivers living with care recipient: 37.4 hours per week Caregivers not living with recipient: 23.7 hours per week Note: Disease-related caregiving is subset of total; includes elderly care, disability care, and child care Additional sources: https://www.aarp.org/caregiving/financial-legal/info-2023/unpaid-caregivers-provide-billions-in-care.html | https://www.bls.gov/news.release/elcare.nr0.htm | https://www.caregiver.org/resource/caregiver-statistics-demographics/

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7.

MMWR, C. Childhood vaccination economic benefits. CDC MMWR https://www.cdc.gov/mmwr/volumes/73/wr/mm7331a2.htm (1994)

US programs (1994-2023): $540B direct savings, $2.7T societal savings ( $18B/year direct,  $90B/year societal) Global (2001-2020): $820B value for 10 diseases in 73 countries ( $41B/year) ROI: $11 return per $1 invested Measles vaccination alone saved 93.7M lives (61% of 154M total) over 50 years (1974-2024) Additional sources: https://www.cdc.gov/mmwr/volumes/73/wr/mm7331a2.htm | https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00850-X/fulltext

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8.

CDC. Childhood vaccination (US) ROI. CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6316a4.htm (2017).

9.

Labor Statistics, U. S. B. of. CPI inflation calculator. (2024)

CPI-U (1980): 82.4 CPI-U (2024): 313.5 Inflation multiplier (1980-2024): 3.80× Cumulative inflation: 280.48% Average annual inflation rate: 3.08% Note: Official U.S. government inflation data using Consumer Price Index for All Urban Consumers (CPI-U). Additional sources: https://www.bls.gov/data/inflation_calculator.htm

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10.

ClinicalTrials.gov API v2 direct analysis. ClinicalTrials.gov cumulative enrollment data (2025). Direct analysis via ClinicalTrials.gov API v2 https://clinicaltrials.gov/data-api/api

Analysis of 100,000 active/recruiting/completed trials on ClinicalTrials.gov (as of January 2025) shows cumulative enrollment of 12.2 million participants: Phase 1 (722k), Phase 2 (2.2M), Phase 3 (6.5M), Phase 4 (2.7M). Median participants per trial: Phase 1 (33), Phase 2 (60), Phase 3 (237), Phase 4 (90). Additional sources: https://clinicaltrials.gov/data-api/api

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11.

CAN, A. Clinical trial patient participation rate. ACS CAN: Barriers to Clinical Trial Enrollment https://www.fightcancer.org/policy-resources/barriers-patient-enrollment-therapeutic-clinical-trials-cancer

Only 3-5% of adult cancer patients in US receive treatment within clinical trials About 5% of American adults have ever participated in any clinical trial Oncology: 2-3% of all oncology patients participate Contrast: 50-60% enrollment for pediatric cancer trials (<15 years old) Note:  20% of cancer trials fail due to insufficient enrollment; 11% of research sites enroll zero patients Additional sources: https://www.fightcancer.org/policy-resources/barriers-patient-enrollment-therapeutic-clinical-trials-cancer | https://hints.cancer.gov/docs/Briefs/HINTS_Brief_48.pdf

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12.

ScienceDaily. Global prevalence of chronic disease. ScienceDaily: GBD 2015 Study https://www.sciencedaily.com/releases/2015/06/150608081753.htm (2015)

2.3 billion individuals had more than five ailments (2013) Chronic conditions caused 74% of all deaths worldwide (2019), up from 67% (2010) Approximately 1 in 3 adults suffer from multiple chronic conditions (MCCs) Risk factor exposures: 2B exposed to biomass fuel, 1B to air pollution, 1B smokers Projected economic cost: $47 trillion by 2030 Note: 2.3B with 5+ ailments is more accurate than "2B with chronic disease." One-third of all adults globally have multiple chronic conditions Additional sources: https://www.sciencedaily.com/releases/2015/06/150608081753.htm | https://pmc.ncbi.nlm.nih.gov/articles/PMC10830426/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6214883/

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13.

C&EN. Annual number of new drugs approved globally:  50. C&EN https://cen.acs.org/pharmaceuticals/50-new-drugs-received-FDA/103/i2 (2025)

50 new drugs approved annually Additional sources: https://cen.acs.org/pharmaceuticals/50-new-drugs-received-FDA/103/i2 | https://www.fda.gov/drugs/development-approval-process-drugs/novel-drug-approvals-fda

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14.

Williams, R. J., Tse, T., DiPiazza, K. & Zarin, D. A. Terminated trials in the ClinicalTrials.gov results database: Evaluation of availability of primary outcome data and reasons for termination. PLOS One 10, e0127242 (2015)

Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Primary reasons: insufficient accrual (57% of non-data-driven terminations), business/strategic reasons, and efficacy/toxicity findings (21% data-driven terminations).

15.

Report, I. Global trial capacity. IQVIA Report: Clinical Trial Subjects Number Drops Due to Decline in COVID-19 Enrollment https://gmdpacademy.org/news/iqvia-report-clinical-trial-subjects-number-drops-due-to-decline-in-covid-19-enrollment/

1.9M participants annually (2022, post-COVID normalization from 4M peak in 2021) Additional sources: https://gmdpacademy.org/news/iqvia-report-clinical-trial-subjects-number-drops-due-to-decline-in-covid-19-enrollment/

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16.

Research & Markets. Global clinical trials market 2024. Research and Markets https://www.globenewswire.com/news-release/2024/04/19/2866012/0/en/Global-Clinical-Trials-Market-Research-Report-2024-An-83-16-Billion-Market-by-2030-AI-Machine-Learning-and-Blockchain-will-Transform-the-Clinical-Trials-Landscape.html (2024)

Global clinical trials market valued at approximately $83 billion in 2024, with projections to reach $83-132 billion by 2030. Additional sources: https://www.globenewswire.com/news-release/2024/04/19/2866012/0/en/Global-Clinical-Trials-Market-Research-Report-2024-An-83-16-Billion-Market-by-2030-AI-Machine-Learning-and-Blockchain-will-Transform-the-Clinical-Trials-Landscape.html | https://www.precedenceresearch.com/clinical-trials-market

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17.

OpenSecrets. Lobbying spend (defense). OpenSecrets https://www.opensecrets.org/industries/lobbying?ind=D (2024).

18.

GiveWell. Cost per DALY for deworming programs. https://www.givewell.org/international/technical/programs/deworming/cost-effectiveness

Schistosomiasis treatment: $28.19-$70.48 per DALY (using arithmetic means with varying disability weights) Soil-transmitted helminths (STH) treatment: $82.54 per DALY (midpoint estimate) Note: GiveWell explicitly states this 2011 analysis is "out of date" and their current methodology focuses on long-term income effects rather than short-term health DALYs Additional sources: https://www.givewell.org/international/technical/programs/deworming/cost-effectiveness

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19.

Transportation, U. S. D. of. Departmental guidance on valuation of a statistical life in economic analysis. (2024).

20.

Think by Numbers. Pre-1962 drug development costs and timeline (think by numbers). Think by Numbers: How Many Lives Does FDA Save? https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ (1962)

Historical estimates (1970-1985): USD $226M fully capitalized (2011 prices) 1980s drugs:  $65M after-tax R&D (1990 dollars),  $194M compounded to approval (1990 dollars) Modern comparison: $2-3B costs, 7-12 years (dramatic increase from pre-1962) Context: 1962 regulatory clampdown reduced new treatment production by 70%, dramatically increasing development timelines and costs Note: Secondary source; less reliable than Congressional testimony Additional sources: https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ | https://en.wikipedia.org/wiki/Cost_of_drug_development | https://www.statnews.com/2018/10/01/changing-1962-law-slash-drug-prices/

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21.

(BIO), B. I. O. BIO clinical development success rates 2011-2020. Biotechnology Innovation Organization (BIO) https://go.bio.org/rs/490-EHZ-999/images/ClinicalDevelopmentSuccessRates2011_2020.pdf (2021)

Phase I duration: 2.3 years average Total time to market (Phase I-III + approval): 10.5 years average Phase transition success rates: Phase I→II: 63.2%, Phase II→III: 30.7%, Phase III→Approval: 58.1% Overall probability of approval from Phase I: 12% Note: Largest publicly available study of clinical trial success rates. Efficacy lag = 10.5 - 2.3 = 8.2 years post-safety verification. Additional sources: https://go.bio.org/rs/490-EHZ-999/images/ClinicalDevelopmentSuccessRates2011_2020.pdf

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22.

Medicine, N. Drug repurposing rate ( 30%). Nature Medicine https://www.nature.com/articles/s41591-024-03233-x (2024)

Approximately 30% of drugs gain at least one new indication after initial approval. Additional sources: https://www.nature.com/articles/s41591-024-03233-x

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23.

EPI. Education investment economic multiplier (2.1). EPI: Public Investments Outside Core Infrastructure https://www.epi.org/publication/bp348-public-investments-outside-core-infrastructure/

Early childhood education: Benefits 12X outlays by 2050; $8.70 per dollar over lifetime Educational facilities: $1 spent → $1.50 economic returns Energy efficiency comparison: 2-to-1 benefit-to-cost ratio (McKinsey) Private return to schooling:  9% per additional year (World Bank meta-analysis) Note: 2.1 multiplier aligns with benefit-to-cost ratios for educational infrastructure/energy efficiency. Early childhood education shows much higher returns (12X by 2050) Additional sources: https://www.epi.org/publication/bp348-public-investments-outside-core-infrastructure/ | https://documents1.worldbank.org/curated/en/442521523465644318/pdf/WPS8402.pdf | https://freopp.org/whitepapers/establishing-a-practical-return-on-investment-framework-for-education-and-skills-development-to-expand-economic-opportunity/

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24.

PMC. Healthcare investment economic multiplier (1.8). PMC: California Universal Health Care https://pmc.ncbi.nlm.nih.gov/articles/PMC5954824/ (2022)

Healthcare fiscal multiplier: 4.3 (95% CI: 2.5-6.1) during pre-recession period (1995-2007) Overall government spending multiplier: 1.61 (95% CI: 1.37-1.86) Why healthcare has high multipliers: No effect on trade deficits (spending stays domestic); improves productivity & competitiveness; enhances long-run potential output Gender-sensitive fiscal spending (health & care economy) produces substantial positive growth impacts Note: "1.8" appears to be conservative estimate; research shows healthcare multipliers of 4.3 Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC5954824/ | https://cepr.org/voxeu/columns/government-investment-and-fiscal-stimulus | https://ncbi.nlm.nih.gov/pmc/articles/PMC3849102/ | https://set.odi.org/wp-content/uploads/2022/01/Fiscal-multipliers-review.pdf

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25.

World Bank. Infrastructure investment economic multiplier (1.6). World Bank: Infrastructure Investment as Stimulus https://blogs.worldbank.org/en/ppps/effectiveness-infrastructure-investment-fiscal-stimulus-what-weve-learned (2022)

Infrastructure fiscal multiplier:  1.6 during contractionary phase of economic cycle Average across all economic states:  1.5 (meaning $1 of public investment → $1.50 of economic activity) Time horizon: 0.8 within 1 year,  1.5 within 2-5 years Range of estimates: 1.5-2.0 (following 2008 financial crisis & American Recovery Act) Italian public construction: 1.5-1.9 multiplier US ARRA: 0.4-2.2 range (differential impacts by program type) Economic Policy Institute: Uses 1.6 for infrastructure spending (middle range of estimates) Note: Public investment less likely to crowd out private activity during recessions; particularly effective when monetary policy loose with near-zero rates Additional sources: https://blogs.worldbank.org/en/ppps/effectiveness-infrastructure-investment-fiscal-stimulus-what-weve-learned | https://www.gihub.org/infrastructure-monitor/insights/fiscal-multiplier-effect-of-infrastructure-investment/ | https://cepr.org/voxeu/columns/government-investment-and-fiscal-stimulus | https://www.richmondfed.org/publications/research/economic_brief/2022/eb_22-04

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26.

Mercatus. Military spending economic multiplier (0.6). Mercatus: Defense Spending and Economy https://www.mercatus.org/research/research-papers/defense-spending-and-economy

Ramey (2011):  0.6 short-run multiplier Barro (1981): 0.6 multiplier for WWII spending (war spending crowded out  40¢ private economic activity per federal dollar) Barro & Redlick (2011): 0.4 within current year, 0.6 over two years; increased govt spending reduces private-sector GDP portions General finding: $1 increase in deficit-financed federal military spending = less than $1 increase in GDP Variation by context: Central/Eastern European NATO: 0.6 on impact, 1.5-1.6 in years 2-3, gradual fall to zero Ramey & Zubairy (2018): Cumulative 1% GDP increase in military expenditure raises GDP by  0.7% Additional sources: https://www.mercatus.org/research/research-papers/defense-spending-and-economy | https://cepr.org/voxeu/columns/world-war-ii-america-spending-deficits-multipliers-and-sacrifice | https://www.rand.org/content/dam/rand/pubs/research_reports/RRA700/RRA739-2/RAND_RRA739-2.pdf

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27.

FDA. FDA-approved prescription drug products (20,000+). FDA https://www.fda.gov/media/143704/download

There are over 20,000 prescription drug products approved for marketing. Additional sources: https://www.fda.gov/media/143704/download

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28.

FDA. FDA GRAS list count ( 570-700). FDA https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory

The FDA GRAS (Generally Recognized as Safe) list contains approximately 570–700 substances. Additional sources: https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory

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29.

ACLED. Active combat deaths annually. ACLED: Global Conflict Surged 2024 https://acleddata.com/2024/12/12/data-shows-global-conflict-surged-in-2024-the-washington-post/ (2024)

2024: 233,597 deaths (30% increase from 179,099 in 2023) Deadliest conflicts: Ukraine (67,000), Palestine (35,000) Nearly 200,000 acts of violence (25% higher than 2023, double from 5 years ago) One in six people globally live in conflict-affected areas Additional sources: https://acleddata.com/2024/12/12/data-shows-global-conflict-surged-in-2024-the-washington-post/ | https://acleddata.com/media-citation/data-shows-global-conflict-surged-2024-washington-post | https://acleddata.com/conflict-index/index-january-2024/

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30.

UCDP. State violence deaths annually. UCDP: Uppsala Conflict Data Program https://ucdp.uu.se/

Uppsala Conflict Data Program (UCDP): Tracks one-sided violence (organized actors attacking unarmed civilians) UCDP definition: Conflicts causing at least 25 battle-related deaths in calendar year 2023 total organized violence: 154,000 deaths; Non-state conflicts: 20,900 deaths UCDP collects data on state-based conflicts, non-state conflicts, and one-sided violence Specific "2,700 annually" figure for state violence not found in recent UCDP data; actual figures vary annually Additional sources: https://ucdp.uu.se/ | https://en.wikipedia.org/wiki/Uppsala_Conflict_Data_Program | https://ourworldindata.org/grapher/deaths-in-armed-conflicts-by-region

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31.

Our World in Data. Terror attack deaths (8,300 annually). Our World in Data: Terrorism https://ourworldindata.org/terrorism (2024)

2023: 8,352 deaths (22% increase from 2022, highest since 2017) 2023: 3,350 terrorist incidents (22% decrease), but 56% increase in avg deaths per attack Global Terrorism Database (GTD): 200,000+ terrorist attacks recorded (2021 version) Maintained by: National Consortium for Study of Terrorism & Responses to Terrorism (START), U. of Maryland Geographic shift: Epicenter moved from Middle East to Central Sahel (sub-Saharan Africa) - now >50% of all deaths Additional sources: https://ourworldindata.org/terrorism | https://reliefweb.int/report/world/global-terrorism-index-2024 | https://www.start.umd.edu/gtd/ | https://ourworldindata.org/grapher/fatalities-from-terrorism

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32.

Institute for Health Metrics and Evaluation (IHME). IHME global burden of disease 2021 (2.88B DALYs, 1.13B YLD). Institute for Health Metrics and Evaluation (IHME) https://vizhub.healthdata.org/gbd-results/ (2024)

In 2021, global DALYs totaled approximately 2.88 billion, comprising 1.75 billion Years of Life Lost (YLL) and 1.13 billion Years Lived with Disability (YLD). This represents a 13% increase from 2019 (2.55B DALYs), largely attributable to COVID-19 deaths and aging populations. YLD accounts for approximately 39% of total DALYs, reflecting the substantial burden of non-fatal chronic conditions. Additional sources: https://vizhub.healthdata.org/gbd-results/ | https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00757-8/fulltext | https://www.healthdata.org/research-analysis/about-gbd

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33.

Costs of War Project, Brown University Watson Institute. Environmental cost of war ($100B annually). Brown Watson Costs of War: Environmental Cost https://watson.brown.edu/costsofwar/costs/social/environment

War on Terror emissions: 1.2B metric tons GHG (equivalent to 257M cars/year) Military: 5.5% of global GHG emissions (2X aviation + shipping combined) US DoD: World’s single largest institutional oil consumer, 47th largest emitter if nation Cleanup costs: $500B+ for military contaminated sites Gaza war environmental damage: $56.4B; landmine clearance: $34.6B expected Climate finance gap: Rich nations spend 30X more on military than climate finance Note: Military activities cause massive environmental damage through GHG emissions, toxic contamination, and long-term cleanup costs far exceeding current climate finance commitments Additional sources: https://watson.brown.edu/costsofwar/costs/social/environment | https://earth.org/environmental-costs-of-wars/ | https://transformdefence.org/transformdefence/stats/

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34.

ScienceDaily. Medical research lives saved annually (4.2 million). ScienceDaily: Physical Activity Prevents 4M Deaths https://www.sciencedaily.com/releases/2020/06/200617194510.htm (2020)

Physical activity: 3.9M early deaths averted annually worldwide (15% lower premature deaths than without) COVID vaccines (2020-2024): 2.533M deaths averted, 14.8M life-years preserved; first year alone: 14.4M deaths prevented Cardiovascular prevention: 3 interventions could delay 94.3M deaths over 25 years (antihypertensives alone: 39.4M) Pandemic research response: Millions of deaths averted through rapid vaccine/drug development Additional sources: https://www.sciencedaily.com/releases/2020/06/200617194510.htm | https://pmc.ncbi.nlm.nih.gov/articles/PMC9537923/ | https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.038160 | https://pmc.ncbi.nlm.nih.gov/articles/PMC9464102/

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35.

SIPRI. 36:1 disparity ratio of spending on weapons over cures. SIPRI: Military Spending https://www.sipri.org/commentary/blog/2016/opportunity-cost-world-military-spending (2016)

Global military spending: $2.7 trillion (2024, SIPRI) Global government medical research:  $68 billion (2024) Actual ratio: 39.7:1 in favor of weapons over medical research Military R&D alone:  $85B (2004 data, 10% of global R&D) Military spending increases crowd out health: 1% ↑ military = 0.62% ↓ health spending Note: Ratio actually worse than 36:1. Each 1% increase in military spending reduces health spending by 0.62%, with effect more intense in poorer countries (0.962% reduction) Additional sources: https://www.sipri.org/commentary/blog/2016/opportunity-cost-world-military-spending | https://pmc.ncbi.nlm.nih.gov/articles/PMC9174441/ | https://www.congress.gov/crs-product/R45403

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36.

Think by Numbers. Lost human capital due to war ($270B annually). Think by Numbers: War Costs $74 https://thinkbynumbers.org/military/war/the-economic-case-for-peace-a-comprehensive-financial-analysis/ (2021)

Lost human capital from war: $300B annually (economic impact of losing skilled/productive individuals to conflict) Broader conflict/violence cost: $14T/year globally 1.4M violent deaths/year; conflict holds back economic development, causes instability, widens inequality, erodes human capital 2002: 48.4M DALYs lost from 1.6M violence deaths = $151B economic value (2000 USD) Economic toll includes: commodity prices, inflation, supply chain disruption, declining output, lost human capital Additional sources: https://thinkbynumbers.org/military/war/the-economic-case-for-peace-a-comprehensive-financial-analysis/ | https://www.weforum.org/stories/2021/02/war-violence-costs-each-human-5-a-day/ | https://pubmed.ncbi.nlm.nih.gov/19115548/

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37.

PubMed. Psychological impact of war cost ($100B annually). PubMed: Economic Burden of PTSD https://pubmed.ncbi.nlm.nih.gov/35485933/

PTSD economic burden (2018 U.S.): $232.2B total ($189.5B civilian, $42.7B military) Civilian costs driven by: Direct healthcare ($66B), unemployment ($42.7B) Military costs driven by: Disability ($17.8B), direct healthcare ($10.1B) Exceeds costs of other mental health conditions (anxiety, depression) War-exposed populations: 2-3X higher rates of anxiety, depression, PTSD; women and children most vulnerable Note: Actual burden $232B, significantly higher than "$100B" claimed Additional sources: https://pubmed.ncbi.nlm.nih.gov/35485933/ | https://news.va.gov/103611/study-national-economic-burden-of-ptsd-staggering/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC9957523/

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38.

CGDev. UNHCR average refugee support cost. CGDev https://www.cgdev.org/blog/costs-hosting-refugees-oecd-countries-and-why-uk-outlier (2024)

The average cost of supporting a refugee is $1,384 per year. This represents total host country costs (housing, healthcare, education, security). OECD countries average $6,100 per refugee (mean 2022-2023), with developing countries spending $700-1,000. Global weighted average of  $1,384 is reasonable given that 75-85% of refugees are in low/middle-income countries. Additional sources: https://www.cgdev.org/blog/costs-hosting-refugees-oecd-countries-and-why-uk-outlier | https://www.unhcr.org/sites/default/files/2024-11/UNHCR-WB-global-cost-of-refugee-inclusion-in-host-country-health-systems.pdf

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39.

World Bank. World bank trade disruption cost from conflict. World Bank https://www.worldbank.org/en/topic/trade/publication/trading-away-from-conflict

Estimated $616B annual cost from conflict-related trade disruption. World Bank research shows civil war costs an average developing country 30 years of GDP growth, with 20 years needed for trade to return to pre-war levels. Trade disputes analysis shows tariff escalation could reduce global exports by up to $674 billion. Additional sources: https://www.worldbank.org/en/topic/trade/publication/trading-away-from-conflict | https://www.nber.org/papers/w11565 | http://blogs.worldbank.org/en/trade/impacts-global-trade-and-income-current-trade-disputes

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40.

VA. Veteran healthcare cost projections. VA https://department.va.gov/wp-content/uploads/2025/06/2026-Budget-in-Brief.pdf (2026)

VA budget: $441.3B requested for FY 2026 (10% increase). Disability compensation: $165.6B in FY 2024 for 6.7M veterans. PACT Act projected to increase spending by $300B between 2022-2031. Costs under Toxic Exposures Fund: $20B (2024), $30.4B (2025), $52.6B (2026). Additional sources: https://department.va.gov/wp-content/uploads/2025/06/2026-Budget-in-Brief.pdf | https://www.cbo.gov/publication/45615 | https://www.legion.org/information-center/news/veterans-healthcare/2025/june/va-budget-tops-400-billion-for-2025-from-higher-spending-on-mandated-benefits-medical-care

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41.

IQVIA Institute for Human Data Science. The global use of medicines 2024: Outlook to 2028. IQVIA Institute Report https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/the-global-use-of-medicines-2024-outlook-to-2028 (2024)

Global days of therapy reached 1.8 trillion in 2019 (234 defined daily doses per person). Diabetes, respiratory, CVD, and cancer account for 71 percent of medicine use. Projected to reach 3.8 trillion DDDs by 2028.

42.

Sinn, M. P. Private industry clinical trial spending estimate. (2025)

Estimated private pharmaceutical and biotech clinical trial spending is approximately $75-90 billion annually, representing roughly 90% of global clinical trial spending.

43.

Calculated from IHME Global Burden of Disease (2.55B DALYs) and global GDP per capita valuation. $109 trillion annual global disease burden.

The global economic burden of disease, including direct healthcare costs ($8.2 trillion) and lost productivity ($100.9 trillion from 2.55 billion DALYs × $39,570 per DALY), totals approximately $109.1 trillion annually.

44.

Sinn, M. P. The Political Dysfunction Tax. https://political-dysfunction-tax.warondisease.org (2025) doi:10.5281/zenodo.18603840

Quantifying the gap between current global governance and theoretical maximum welfare, estimating a 31-53% efficiency score and $97 trillion in annual opportunity costs.

45.

Trials, A. C. Global government spending on interventional clinical trials:  $3-6 billion/year. Applied Clinical Trials https://www.appliedclinicaltrialsonline.com/view/sizing-clinical-research-market

Estimated range based on NIH ( $0.8-5.6B), NIHR ($1.6B total budget), and EU funding ( $1.3B/year). Roughly 5-10% of global market. Additional sources: https://www.appliedclinicaltrialsonline.com/view/sizing-clinical-research-market | https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30357-0/fulltext

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46.

UBS. Credit suisse global wealth report 2023. Credit Suisse/UBS https://www.ubs.com/global/en/family-office-uhnw/reports/global-wealth-report-2023.html (2023)

Total global household wealth: USD 454.4 trillion (2022) Wealth declined by USD 11.3 trillion (-2.4%) in 2022, first decline since 2008 Wealth per adult: USD 84,718 Additional sources: https://www.ubs.com/global/en/family-office-uhnw/reports/global-wealth-report-2023.html

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47.

Component country budgets. Global government medical research spending ($67.5B, 2023–2024). See component country budgets: NIH Budget https://www.nih.gov/about-nih/what-we-do/budget.

48.

SIPRI. Global military spending ($2.72T, 2024). SIPRI https://www.sipri.org/publications/2025/sipri-fact-sheets/trends-world-military-expenditure-2024 (2025).

49.

Estimated from major foundation budgets and activities. Nonprofit clinical trial funding estimate.

Nonprofit foundations spend an estimated $2-5 billion annually on clinical trials globally, representing approximately 2-5% of total clinical trial spending.

50.

IQVIA, I. reports: Global pharmaceutical r&d spending.

Total global pharmaceutical R&D spending is approximately $300 billion annually. Clinical trials represent 15-20% of this total ($45-60B), with the remainder going to drug discovery, preclinical research, regulatory affairs, and manufacturing development.

51.

UN. Global population reaches 8 billion. UN: World Population 8 Billion Nov 15 2022 https://www.un.org/en/desa/world-population-reach-8-billion-15-november-2022 (2022)

Milestone: November 15, 2022 (UN World Population Prospects 2022) Day of Eight Billion" designated by UN Added 1 billion people in just 11 years (2011-2022) Growth rate: Slowest since 1950; fell under 1% in 2020 Future: 15 years to reach 9B (2037); projected peak 10.4B in 2080s Projections: 8.5B (2030), 9.7B (2050), 10.4B (2080-2100 plateau) Note: Milestone reached Nov 2022. Population growth slowing; will take longer to add next billion (15 years vs 11 years) Additional sources: https://www.un.org/en/desa/world-population-reach-8-billion-15-november-2022 | https://www.un.org/en/dayof8billion | https://en.wikipedia.org/wiki/Day_of_Eight_Billion

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52.

Harvard Kennedy School. 3.5% participation tipping point. Harvard Kennedy School https://www.hks.harvard.edu/centers/carr/publications/35-rule-how-small-minority-can-change-world (2020)

The research found that nonviolent campaigns were twice as likely to succeed as violent ones, and once 3.5% of the population were involved, they were always successful. Chenoweth and Maria Stephan studied the success rates of civil resistance efforts from 1900 to 2006, finding that nonviolent movements attracted, on average, four times as many participants as violent movements and were more likely to succeed. Key finding: Every campaign that mobilized at least 3.5% of the population in sustained protest was successful (in their 1900-2006 dataset) Note: The 3.5% figure is a descriptive statistic from historical analysis, not a guaranteed threshold. One exception (Bahrain 2011-2014 with 6%+ participation) has been identified. The rule applies to regime change, not policy change in democracies. Additional sources: https://www.hks.harvard.edu/centers/carr/publications/35-rule-how-small-minority-can-change-world | https://www.hks.harvard.edu/sites/default/files/2024-05/Erica%20Chenoweth_2020-005.pdf | https://www.bbc.com/future/article/20190513-it-only-takes-35-of-people-to-change-the-world | https://en.wikipedia.org/wiki/3.5%25_rule

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53.

NHGRI. Human genome project and CRISPR discovery. NHGRI https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp (2003)

Your DNA is 3 billion base pairs Read the entire code (Human Genome Project, completed 2003) Learned to edit it (CRISPR, discovered 2012) Additional sources: https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp | https://www.nobelprize.org/prizes/chemistry/2020/press-release/

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54.

PMC. Only  12% of human interactome targeted. PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC10749231/ (2023)

Mapping 350,000+ clinical trials showed that only  12% of the human interactome has ever been targeted by drugs. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC10749231/

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55.

WHO. ICD-10 code count ( 14,000). WHO https://icd.who.int/browse10/2019/en (2019)

The ICD-10 classification contains approximately 14,000 codes for diseases, signs and symptoms. Additional sources: https://icd.who.int/browse10/2019/en

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56.

Wikipedia. Longevity escape velocity (LEV) - maximum human life extension potential. Wikipedia: Longevity Escape Velocity https://en.wikipedia.org/wiki/Longevity_escape_velocity

Longevity escape velocity: Hypothetical point where medical advances extend life expectancy faster than time passes Term coined by Aubrey de Grey (biogerontologist) in 2004 paper; concept from David Gobel (Methuselah Foundation) Current progress: Science adds  3 months to lifespan per year; LEV requires adding >1 year per year Sinclair (Harvard): "There is no biological upper limit to age" - first person to live to 150 may already be born De Grey: 50% chance of reaching LEV by mid-to-late 2030s; SENS approach = damage repair rather than slowing damage Kurzweil (2024): LEV by 2029-2035, AI will simulate biological processes to accelerate solutions George Church: LEV "in a decade or two" via age-reversal clinical trials Natural lifespan cap:  120-150 years (Jeanne Calment record: 122); engineering approach could bypass via damage repair Key mechanisms: Epigenetic reprogramming, senolytic drugs, stem cell therapy, gene therapy, AI-driven drug discovery Current record: Jeanne Calment (122 years, 164 days) - record unbroken since 1997 Note: LEV is theoretical but increasingly plausible given demonstrated age reversal in mice (109% lifespan extension) and human cells (30-year epigenetic age reversal) Additional sources: https://en.wikipedia.org/wiki/Longevity_escape_velocity | https://pmc.ncbi.nlm.nih.gov/articles/PMC423155/ | https://www.popularmechanics.com/science/a36712084/can-science-cure-death-longevity/ | https://www.diamandis.com/blog/longevity-escape-velocity

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57.

OpenSecrets. Lobbyist statistics for washington d.c. OpenSecrets: Lobbying in US https://en.wikipedia.org/wiki/Lobbying_in_the_United_States

Registered lobbyists: Over 12,000 (some estimates); 12,281 registered (2013) Former government employees as lobbyists: 2,200+ former federal employees (1998-2004), including 273 former White House staffers,  250 former Congress members & agency heads Congressional revolving door: 43% (86 of 198) lawmakers who left 1998-2004 became lobbyists; currently 59% leaving to private sector work for lobbying/consulting firms/trade groups Executive branch: 8% were registered lobbyists at some point before/after government service Additional sources: https://en.wikipedia.org/wiki/Lobbying_in_the_United_States | https://www.opensecrets.org/revolving-door | https://www.citizen.org/article/revolving-congress/ | https://www.propublica.org/article/we-found-a-staggering-281-lobbyists-whove-worked-in-the-trump-administration

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58.

Vaccines, M. Measles vaccination ROI. MDPI Vaccines https://www.mdpi.com/2076-393X/12/11/1210 (2024)

Single measles vaccination: 167:1 benefit-cost ratio. MMR (measles-mumps-rubella) vaccination: 14:1 ROI. Historical US elimination efforts (1966-1974): benefit-cost ratio of 10.3:1 with net benefits exceeding USD 1.1 billion (1972 dollars, or USD 8.0 billion in 2023 dollars). 2-dose MMR programs show direct benefit/cost ratio of 14.2 with net savings of $5.3 billion, and 26.0 from societal perspectives with net savings of $11.6 billion. Additional sources: https://www.mdpi.com/2076-393X/12/11/1210 | https://www.tandfonline.com/doi/full/10.1080/14760584.2024.2367451

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59.

Gosse, M. E. Assessing cost-effectiveness in healthcare: History of the $50,000 per QALY threshold. Sustainability Impact Metrics https://ecocostsvalue.com/EVR/img/references%20others/Gosse%202008%20QALY%20threshold%20financial.pdf (2008).

60.

World Health Organization. Mental health global burden. World Health Organization https://www.who.int/news/item/28-09-2001-the-world-health-report-2001-mental-disorders-affect-one-in-four-people (2022)

One in four people in the world will be affected by mental or neurological disorders at some point in their lives, representing [approximately] 30% of the global burden of disease. Additional sources: https://www.who.int/news/item/28-09-2001-the-world-health-report-2001-mental-disorders-affect-one-in-four-people

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61.

Institute, S. I. P. R. Trends in world military expenditure, 2023. (2024).

62.

Calculated from Orphanet Journal of Rare Diseases (2024). Diseases getting first effective treatment each year. Calculated from Orphanet Journal of Rare Diseases (2024) https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03398-1 (2024)

Under the current system, approximately 10-15 diseases per year receive their FIRST effective treatment. Calculation: 5% of 7,000 rare diseases ( 350) have FDA-approved treatment, accumulated over 40 years of the Orphan Drug Act =  9 rare diseases/year. Adding  5-10 non-rare diseases that get first treatments yields  10-20 total. FDA approves  50 drugs/year, but many are for diseases that already have treatments (me-too drugs, second-line therapies). Only  15 represent truly FIRST treatments for previously untreatable conditions.

63.

NIH. NIH budget (FY 2025). NIH https://www.nih.gov/about-nih/organization/budget (2024)

The budget total of $47.7 billion also includes $1.412 billion derived from PHS Evaluation financing... Additional sources: https://www.nih.gov/about-nih/organization/budget | https://officeofbudget.od.nih.gov/

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64.

Bentley et al. NIH spending on clinical trials:  3.3%. Bentley et al. https://pmc.ncbi.nlm.nih.gov/articles/PMC10349341/ (2023)

NIH spent $8.1 billion on clinical trials for approved drugs (2010-2019), representing 3.3% of relevant NIH spending. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC10349341/ | https://catalyst.harvard.edu/news/article/nih-spent-8-1b-for-phased-clinical-trials-of-drugs-approved-2010-19-10-of-reported-industry-spending/

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65.

PMC. Standard medical research ROI ($20k-$100k/QALY). PMC: Cost-effectiveness Thresholds Used by Study Authors https://pmc.ncbi.nlm.nih.gov/articles/PMC10114019/ (1990)

Typical cost-effectiveness thresholds for medical interventions in rich countries range from $50,000 to $150,000 per QALY. The Institute for Clinical and Economic Review (ICER) uses a $100,000-$150,000/QALY threshold for value-based pricing. Between 1990-2021, authors increasingly cited $100,000 (47% by 2020-21) or $150,000 (24% by 2020-21) per QALY as benchmarks for cost-effectiveness. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC10114019/ | https://icer.org/our-approach/methods-process/cost-effectiveness-the-qaly-and-the-evlyg/

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66.

Institute, M. RECOVERY trial 82× cost reduction. Manhattan Institute: Slow Costly Trials https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs

RECOVERY trial:  $500 per patient ($20M for 48,000 patients = $417/patient) Typical clinical trial:  $41,000 median per-patient cost Cost reduction:  80-82× cheaper ($41,000 ÷ $500 ≈ 82×) Efficiency: $50 per patient per answer (10 therapeutics tested, 4 effective) Dexamethasone estimated to save >630,000 lives Additional sources: https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs | https://pmc.ncbi.nlm.nih.gov/articles/PMC9293394/

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67.

Trials. Patient willingness to participate in clinical trials. Trials: Patients’ Willingness Survey https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-1105-3

Recent surveys: 49-51% willingness (2020-2022) - dramatic drop from 85% (2019) during COVID-19 pandemic Cancer patients when approached: 88% consented to trials (Royal Marsden Hospital) Study type variation: 44.8% willing for drug trial, 76.2% for diagnostic study Top motivation: "Learning more about my health/medical condition" (67.4%) Top barrier: "Worry about experiencing side effects" (52.6%) Additional sources: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-1105-3 | https://www.appliedclinicaltrialsonline.com/view/industry-forced-to-rethink-patient-participation-in-trials | https://pmc.ncbi.nlm.nih.gov/articles/PMC7183682/

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68.

CSDD, T. Cost of drug development.

Various estimates suggest $1.0 - $2.5 billion to bring a new drug from discovery through FDA approval, spread across  10 years. Tufts Center for the Study of Drug Development often cited for $1.0 - $2.6 billion/drug. Industry reports (IQVIA, Deloitte) also highlight $2+ billion figures.

69.

Value in Health. Average lifetime revenue per successful drug. Value in Health: Sales Revenues for New Therapeutic Agents https://www.sciencedirect.com/science/article/pii/S1098301524027542

Study of 361 FDA-approved drugs from 1995-2014 (median follow-up 13.2 years): Mean lifetime revenue: $15.2 billion per drug Median lifetime revenue: $6.7 billion per drug Revenue after 5 years: $3.2 billion (mean) Revenue after 10 years: $9.5 billion (mean) Revenue after 15 years: $19.2 billion (mean) Distribution highly skewed: top 25 drugs (7%) accounted for 38% of total revenue ($2.1T of $5.5T) Additional sources: https://www.sciencedirect.com/science/article/pii/S1098301524027542

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70.

Lichtenberg, F. R. How many life-years have new drugs saved? A three-way fixed-effects analysis of 66 diseases in 27 countries, 2000-2013. International Health 11, 403–416 (2019)

Using 3-way fixed-effects methodology (disease-country-year) across 66 diseases in 22 countries, this study estimates that drugs launched after 1981 saved 148.7 million life-years in 2013 alone. The regression coefficients for drug launches 0-11 years prior (beta=-0.031, SE=0.008) and 12+ years prior (beta=-0.057, SE=0.013) on years of life lost are highly significant (p<0.0001). Confidence interval for life-years saved: 79.4M-239.8M (95 percent CI) based on propagated standard errors from Table 2.

71.

Deloitte. Pharmaceutical r&d return on investment (ROI). Deloitte: Measuring Pharmaceutical Innovation 2025 https://www.deloitte.com/ch/en/Industries/life-sciences-health-care/research/measuring-return-from-pharmaceutical-innovation.html (2025)

Deloitte’s annual study of top 20 pharma companies by R&D spend (2010-2024): 2024 ROI: 5.9% (second year of growth after decade of decline) 2023 ROI:  4.3% (estimated from trend) 2022 ROI: 1.2% (historic low since study began, 13-year low) 2021 ROI: 6.8% (record high, inflated by COVID-19 vaccines/treatments) Long-term trend: Declining for over a decade before 2023 recovery Average R&D cost per asset: $2.3B (2022), $2.23B (2024) These returns (1.2-5.9% range) fall far below typical corporate ROI targets (15-20%) Additional sources: https://www.deloitte.com/ch/en/Industries/life-sciences-health-care/research/measuring-return-from-pharmaceutical-innovation.html | https://www.prnewswire.com/news-releases/deloittes-13th-annual-pharmaceutical-innovation-report-pharma-rd-return-on-investment-falls-in-post-pandemic-market-301738807.html | https://hitconsultant.net/2023/02/16/pharma-rd-roi-falls-to-lowest-level-in-13-years/

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72.

Nature Reviews Drug Discovery. Drug trial success rate from phase i to approval. Nature Reviews Drug Discovery: Clinical Success Rates https://www.nature.com/articles/nrd.2016.136 (2016)

Overall Phase I to approval: 10-12.8% (conventional wisdom  10%, studies show 12.8%) Recent decline: Average LOA now 6.7% for Phase I (2014-2023 data) Leading pharma companies: 14.3% average LOA (range 8-23%) Varies by therapeutic area: Oncology 3.4%, CNS/cardiovascular lowest at Phase III Phase-specific success: Phase I 47-54%, Phase II 28-34%, Phase III 55-70% Note: 12% figure accurate for historical average. Recent data shows decline to 6.7%, with Phase II as primary attrition point (28% success) Additional sources: https://www.nature.com/articles/nrd.2016.136 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6409418/ | https://academic.oup.com/biostatistics/article/20/2/273/4817524

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73.

SofproMed. Phase 3 cost per trial range. SofproMed https://www.sofpromed.com/how-much-does-a-clinical-trial-cost

Phase 3 clinical trials cost between $20 million and $282 million per trial, with significant variation by therapeutic area and trial complexity. Additional sources: https://www.sofpromed.com/how-much-does-a-clinical-trial-cost | https://www.cbo.gov/publication/57126

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74.

Ramsberg J, P. R. Pragmatic trial cost per patient (median $97). Learning Health Systems https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/ (2018)

Meta-analysis of 108 embedded pragmatic clinical trials (2006-2016). The median cost per patient was $97 (IQR $19–$478), based on 2015 dollars. 25% of trials cost <$19/patient; 10 trials exceeded $1,000/patient. U.S. studies median $187 vs non-U.S. median $27. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/

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75.

WHO. Polio vaccination ROI. WHO https://www.who.int/news-room/feature-stories/detail/sustaining-polio-investments-offers-a-high-return (2019)

For every dollar spent, the return on investment is nearly US$ 39." Total investment cost of US$ 7.5 billion generates projected economic and social benefits of US$ 289.2 billion from sustaining polio assets and integrating them into expanded immunization, surveillance and emergency response programmes across 8 priority countries (Afghanistan, Iraq, Libya, Pakistan, Somalia, Sudan, Syria, Yemen). Additional sources: https://www.who.int/news-room/feature-stories/detail/sustaining-polio-investments-offers-a-high-return

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76.

ICRC. International campaign to ban landmines (ICBL) - ottawa treaty (1997). ICRC https://www.icrc.org/en/doc/resources/documents/article/other/57jpjn.htm (1997)

ICBL: Founded 1992 by 6 NGOs (Handicap International, Human Rights Watch, Medico International, Mines Advisory Group, Physicians for Human Rights, Vietnam Veterans of America Foundation) Started with ONE staff member: Jody Williams as founding coordinator Grew to 1,000+ organizations in 60 countries by 1997 Ottawa Process: 14 months (October 1996 - December 1997) Convention signed by 122 states on December 3, 1997; entered into force March 1, 1999 Achievement: Nobel Peace Prize 1997 (shared by ICBL and Jody Williams) Government funding context: Canada established $100M CAD Canadian Landmine Fund over 10 years (1997); International donors provided $169M in 1997 for mine action (up from $100M in 1996) Additional sources: https://www.icrc.org/en/doc/resources/documents/article/other/57jpjn.htm | https://en.wikipedia.org/wiki/International_Campaign_to_Ban_Landmines | https://www.nobelprize.org/prizes/peace/1997/summary/ | https://un.org/press/en/1999/19990520.MINES.BRF.html | https://www.the-monitor.org/en-gb/reports/2003/landmine-monitor-2003/mine-action-funding.aspx

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77.

OpenSecrets. Revolving door: Former members of congress. (2024)

388 former members of Congress are registered as lobbyists. Nearly 5,400 former congressional staffers have left Capitol Hill to become federal lobbyists in the past 10 years. Additional sources: https://www.opensecrets.org/revolving-door

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78.

Kinch, M. S. & Griesenauer, R. H. Lost medicines: A longer view of the pharmaceutical industry with the potential to reinvigorate discovery. Drug Discovery Today 24, 875–880 (2019)

Research identified 1,600+ medicines available in 1962. The 1950s represented industry high-water mark with >30 new products in five of ten years; this rate would not be replicated until late 1990s. More than half (880) of these medicines were lost following implementation of Kefauver-Harris Amendment. The peak of 1962 would not be seen again until early 21st century. By 2016 number of organizations actively involved in R&D at level not seen since 1914.

79.

Wikipedia. US military spending reduction after WWII. Wikipedia https://en.wikipedia.org/wiki/Demobilization_of_United_States_Armed_Forces_after_World_War_II (2020)

Peaking at over $81 billion in 1945, the U.S. military budget plummeted to approximately $13 billion by 1948, representing an 84% decrease. The number of personnel was reduced almost 90%, from more than 12 million to about 1.5 million between mid-1945 and mid-1947. Defense spending exceeded 41 percent of GDP in 1945. After World War II, the US reduced military spending to 7.2 percent of GDP by 1948. Defense spending doubled from the 1948 low to 15 percent at the height of the Korean War in 1953. Additional sources: https://en.wikipedia.org/wiki/Demobilization_of_United_States_Armed_Forces_after_World_War_II | https://www.americanprogress.org/article/a-historical-perspective-on-military-budgets/ | https://www.stlouisfed.org/on-the-economy/2020/february/war-highest-military-spending-measured | https://www.usgovernmentspending.com/defense_spending_history

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80.

Baily, M. N. Pre-1962 drug development costs (baily 1972). Baily (1972) https://samizdathealth.org/wp-content/uploads/2020/12/hlthaff.1.2.6.pdf (1972)

Pre-1962: Average cost per new chemical entity (NCE) was $6.5 million (1980 dollars) Inflation-adjusted to 2024 dollars: $6.5M (1980) ≈ $22.5M (2024), using CPI multiplier of 3.46× Real cost increase (inflation-adjusted): $22.5M (pre-1962) → $2,600M (2024) = 116× increase Note: This represents the most comprehensive academic estimate of pre-1962 drug development costs based on empirical industry data Additional sources: https://samizdathealth.org/wp-content/uploads/2020/12/hlthaff.1.2.6.pdf

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81.

Think by Numbers. Pre-1962 physician-led clinical trials. Think by Numbers: How Many Lives Does FDA Save? https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ (1966)

Pre-1962: Physicians could report real-world evidence directly 1962 Drug Amendments replaced "premarket notification" with "premarket approval", requiring extensive efficacy testing Impact: New regulatory clampdown reduced new treatment production by 70%; lifespan growth declined from  4 years/decade to  2 years/decade Drug Efficacy Study Implementation (DESI): NAS/NRC evaluated 3,400+ drugs approved 1938-1962 for safety only; reviewed >3,000 products, >16,000 therapeutic claims FDA has had authority to accept real-world evidence since 1962, clarified by 21st Century Cures Act (2016) Note: Specific "144,000 physicians" figure not verified in sources Additional sources: https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ | https://www.fda.gov/drugs/enforcement-activities-fda/drug-efficacy-study-implementation-desi | http://www.nasonline.org/about-nas/history/archives/collections/des-1966-1969-1.html

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82.

GAO. 95% of diseases have 0 FDA-approved treatments. GAO https://www.gao.gov/products/gao-25-106774 (2025)

95% of diseases have no treatment Additional sources: https://www.gao.gov/products/gao-25-106774 | https://globalgenes.org/rare-disease-facts/

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83.

Oren Cass, M. I. RECOVERY trial cost per patient. Oren Cass https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs (2023)

The RECOVERY trial, for example, cost only about $500 per patient... By contrast, the median per-patient cost of a pivotal trial for a new therapeutic is around $41,000. Additional sources: https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs

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84.

al., N. E. Á. et. RECOVERY trial global lives saved ( 1 million). NHS England: 1 Million Lives Saved https://www.england.nhs.uk/2021/03/covid-treatment-developed-in-the-nhs-saves-a-million-lives/ (2021)

Dexamethasone saved  1 million lives worldwide (NHS England estimate, March 2021, 9 months after discovery). UK alone: 22,000 lives saved. Methodology: Águas et al. Nature Communications 2021 estimated 650,000 lives (range: 240,000-1,400,000) for July-December 2020 alone, based on RECOVERY trial mortality reductions (36% for ventilated, 18% for oxygen-only patients) applied to global COVID hospitalizations. June 2020 announcement: Dexamethasone reduced deaths by up to 1/3 (ventilated patients), 1/5 (oxygen patients). Impact immediate: Adopted into standard care globally within hours of announcement. Additional sources: https://www.england.nhs.uk/2021/03/covid-treatment-developed-in-the-nhs-saves-a-million-lives/ | https://www.nature.com/articles/s41467-021-21134-2 | https://pharmaceutical-journal.com/article/news/steroid-has-saved-the-lives-of-one-million-covid-19-patients-worldwide-figures-show | https://www.recoverytrial.net/news/recovery-trial-celebrates-two-year-anniversary-of-life-saving-dexamethasone-result

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85.

Museum, N. S. 11. M. &. September 11 attack facts. (2024)

2,977 people were killed in the September 11, 2001 attacks: 2,753 at the World Trade Center, 184 at the Pentagon, and 40 passengers and crew on United Flight 93 in Shanksville, Pennsylvania.

86.

World Bank. World bank singapore economic data. World Bank https://data.worldbank.org/country/singapore (2024)

Singapore GDP per capita (2023): $82,000 - among highest in the world Government spending: 15% of GDP (vs US 38%) Life expectancy: 84.1 years (vs US 77.5 years) Singapore demonstrates that low government spending can coexist with excellent outcomes Additional sources: https://data.worldbank.org/country/singapore

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87.

Fund, I. M. IMF singapore government spending data. (2024)

Singapore government spending is approximately 15% of GDP This is 23 percentage points lower than the United States (38%) Despite lower spending, Singapore achieves excellent outcomes: - Life expectancy: 84.1 years (vs US 77.5) - Low crime, world-class infrastructure, AAA credit rating Additional sources: https://www.imf.org/en/Countries/SGP

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88.

World Health Organization. WHO life expectancy data by country. (2024)

Life expectancy at birth varies significantly among developed nations: Switzerland: 84.0 years (2023) Singapore: 84.1 years (2023) Japan: 84.3 years (2023) United States: 77.5 years (2023) - 6.5 years below Switzerland, Singapore Global average:  73 years Note: US spends more per capita on healthcare than any other nation, yet achieves lower life expectancy Additional sources: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-life-expectancy-and-healthy-life-expectancy

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89.

CSIS. Smallpox eradication ROI. CSIS https://www.csis.org/analysis/smallpox-eradication-model-global-cooperation.

90.

PMC. Contribution of smoking reduction to life expectancy gains. PMC: Benefits Smoking Cessation Longevity https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447499/ (2012)

Population-level: Up to 14% (9% men, 14% women) of total life expectancy gain since 1960 due to tobacco control efforts Individual cessation benefits: Quitting at age 35 adds 6.9-8.5 years (men), 6.1-7.7 years (women) vs continuing smokers By cessation age: Age 25-34 = 10 years gained; age 35-44 = 9 years; age 45-54 = 6 years; age 65 = 2.0 years (men), 3.7 years (women) Cessation before age 40: Reduces death risk by  90% Long-term cessation: 10+ years yields survival comparable to never smokers, averts  10 years of life lost Recent cessation: <3 years averts  5 years of life lost Additional sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447499/ | https://www.cdc.gov/pcd/issues/2012/11_0295.htm | https://www.ajpmonline.org/article/S0749-3797(24)00217-4/fulltext | https://www.nejm.org/doi/full/10.1056/NEJMsa1211128

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91.

ICER. Value per QALY (standard economic value). ICER https://icer.org/wp-content/uploads/2024/02/Reference-Case-4.3.25.pdf (2024)

Standard economic value per QALY: $100,000–$150,000. This is the US and global standard willingness-to-pay threshold for interventions that add costs. Dominant interventions (those that save money while improving health) are favorable regardless of this threshold. Additional sources: https://icer.org/wp-content/uploads/2024/02/Reference-Case-4.3.25.pdf

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92.

GAO. Annual cost of u.s. Sugar subsidies. GAO: Sugar Program https://www.gao.gov/products/gao-24-106144

Consumer costs: $2.5-3.5 billion per year (GAO estimate) Net economic cost:  $1 billion per year 2022: US consumers paid 2X world price for sugar Program costs $3-4 billion/year but no federal budget impact (costs passed directly to consumers via higher prices) Employment impact: 10,000-20,000 manufacturing jobs lost annually in sugar-reliant industries (confectionery, etc.) Multiple studies confirm: Sweetener Users Association ($2.9-3.5B), AEI ($2.4B consumer cost), Beghin & Elobeid ($2.9-3.5B consumer surplus) Additional sources: https://www.gao.gov/products/gao-24-106144 | https://www.heritage.org/agriculture/report/the-us-sugar-program-bad-consumers-bad-agriculture-and-bad-america | https://www.aei.org/articles/the-u-s-spends-4-billion-a-year-subsidizing-stalinist-style-domestic-sugar-production/

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93.

World Bank. Swiss military budget as percentage of GDP. World Bank: Military Expenditure https://data.worldbank.org/indicator/MS.MIL.XPND.GD.ZS?locations=CH

2023: 0.70272% of GDP (World Bank) 2024: CHF 5.95 billion official military spending When including militia system costs:  1% GDP (CHF 8.75B) Comparison: Near bottom in Europe; only Ireland, Malta, Moldova spend less (excluding microstates with no armies) Additional sources: https://data.worldbank.org/indicator/MS.MIL.XPND.GD.ZS?locations=CH | https://www.avenir-suisse.ch/en/blog-defence-spending-switzerland-is-in-better-shape-than-it-seems/ | https://tradingeconomics.com/switzerland/military-expenditure-percent-of-gdp-wb-data.html

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94.

World Bank. Switzerland vs. US GDP per capita comparison. World Bank: Switzerland GDP Per Capita https://data.worldbank.org/indicator/NY.GDP.PCAP.CD?locations=CH

2024 GDP per capita (PPP-adjusted): Switzerland $93,819 vs United States $75,492 Switzerland’s GDP per capita 24% higher than US when adjusted for purchasing power parity Nominal 2024: Switzerland $103,670 vs US $85,810 Additional sources: https://data.worldbank.org/indicator/NY.GDP.PCAP.CD?locations=CH | https://tradingeconomics.com/switzerland/gdp-per-capita-ppp | https://www.theglobaleconomy.com/USA/gdp_per_capita_ppp/

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95.

OECD. OECD government spending as percentage of GDP. (2024)

OECD government spending data shows significant variation among developed nations: United States: 38.0% of GDP (2023) Switzerland: 35.0% of GDP - 3 percentage points lower than US Singapore: 15.0% of GDP - 23 percentage points lower than US (per IMF data) OECD average: approximately 40% of GDP Additional sources: https://data.oecd.org/gga/general-government-spending.htm

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96.

OECD. OECD median household income comparison. (2024)

Median household disposable income varies significantly across OECD nations: United States: $77,500 (2023) Switzerland: $55,000 PPP-adjusted (lower nominal but comparable purchasing power) Singapore: $75,000 PPP-adjusted Additional sources: https://data.oecd.org/hha/household-disposable-income.htm

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97.

Institute, C. Chance of dying from terrorism statistic. Cato Institute: Terrorism and Immigration Risk Analysis https://www.cato.org/policy-analysis/terrorism-immigration-risk-analysis

Chance of American dying in foreign-born terrorist attack: 1 in 3.6 million per year (1975-2015) Including 9/11 deaths; annual murder rate is 253x higher than terrorism death rate More likely to die from lightning strike than foreign terrorism Note: Comprehensive 41-year study shows terrorism risk is extremely low compared to everyday dangers Additional sources: https://www.cato.org/policy-analysis/terrorism-immigration-risk-analysis | https://www.nbcnews.com/news/us-news/you-re-more-likely-die-choking-be-killed-foreign-terrorists-n715141

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98.

Wikipedia. Thalidomide scandal: Worldwide cases and mortality. Wikipedia https://en.wikipedia.org/wiki/Thalidomide_scandal

The total number of embryos affected by the use of thalidomide during pregnancy is estimated at 10,000, of whom about 40% died around the time of birth. More than 10,000 children in 46 countries were born with deformities such as phocomelia. Additional sources: https://en.wikipedia.org/wiki/Thalidomide_scandal

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99.

One, P. Health and quality of life of thalidomide survivors as they age. PLOS One https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210222 (2019)

Study of thalidomide survivors documenting ongoing disability impacts, quality of life, and long-term health outcomes. Survivors (now in their 60s) continue to experience significant disability from limb deformities, organ damage, and other effects. Additional sources: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210222

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100.

Bureau, U. C. Historical world population estimates. US Census Bureau https://www.census.gov/data/tables/time-series/demo/international-programs/historical-est-worldpop.html

US Census Bureau historical estimates of world population by country and region (1950-2050). US population in 1960:  180 million of  3 billion worldwide (6%). Additional sources: https://www.census.gov/data/tables/time-series/demo/international-programs/historical-est-worldpop.html

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101.

FDA Study via NCBI. Trial costs, FDA study. FDA Study via NCBI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248200/

Overall, the 138 clinical trials had an estimated median (IQR) cost of $19.0 million ($12.2 million-$33.1 million)... The clinical trials cost a median (IQR) of $41,117 ($31,802-$82,362) per patient. Additional sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248200/

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102.

Diseases, G. 2019. & Collaborators, I. Global burden of disease study 2019: Disability weights. The Lancet 396, 1204–1222 (2020)

Disability weights for 235 health states used in Global Burden of Disease calculations. Weights range from 0 (perfect health) to 1 (death equivalent). Chronic conditions like diabetes (0.05-0.35), COPD (0.04-0.41), depression (0.15-0.66), and cardiovascular disease (0.04-0.57) show substantial variation by severity. Treatment typically reduces disability weights by 50-80 percent for manageable chronic conditions.

103.

WHO. Annual global economic burden of alzheimer’s and other dementias. WHO: Dementia Fact Sheet https://www.who.int/news-room/fact-sheets/detail/dementia (2019)

Global cost: $1.3 trillion (2019 WHO-commissioned study) 50% from informal caregivers (family/friends,  5 hrs/day) 74% of costs in high-income countries despite 61% of patients in LMICs $818B (2010) → $1T (2018) → $1.3T (2019) - rapid growth Note: Costs increased 35% from 2010-2015 alone. Informal care represents massive hidden economic burden Additional sources: https://www.who.int/news-room/fact-sheets/detail/dementia | https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12901

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104.

Oncology, J. Annual global economic burden of cancer. JAMA Oncology: Global Cost 2020-2050 https://jamanetwork.com/journals/jamaoncology/fullarticle/2801798 (2020)

2020-2050 projection: $25.2 trillion total ($840B/year average) 2010 annual cost: $1.16 trillion (direct costs only) Recent estimate:  $3 trillion/year (all costs included) Top 5 cancers: lung (15.4%), colon/rectum (10.9%), breast (7.7%), liver (6.5%), leukemia (6.3%) Note: China/US account for 45% of global burden; 75% of deaths in LMICs but only 50.0% of economic cost Additional sources: https://jamanetwork.com/journals/jamaoncology/fullarticle/2801798 | https://www.nature.com/articles/d41586-023-00634-9

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105.

CDC. U.s. Chronic disease healthcare spending. CDC https://www.cdc.gov/chronic-disease/data-research/facts-stats/index.html

Chronic diseases account for  90% of U.S. healthcare spending ( $3.7T/year). Additional sources: https://www.cdc.gov/chronic-disease/data-research/facts-stats/index.html

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106.

Care, D. Annual global economic burden of diabetes. Diabetes Care: Global Economic Burden https://diabetesjournals.org/care/article/41/5/963/36522/Global-Economic-Burden-of-Diabetes-in-Adults

2015: $1.3 trillion (1.8% of global GDP) 2030 projections: $2.1T-2.5T depending on scenario IDF health expenditure: $760B (2019) → $845B (2045 projected) 2/3 direct medical costs ($857B), 1/3 indirect costs (lost productivity) Note: Costs growing rapidly; expected to exceed $2T by 2030 Additional sources: https://diabetesjournals.org/care/article/41/5/963/36522/Global-Economic-Burden-of-Diabetes-in-Adults | https://doi.org/10.1016/S2213-8587(17)30097-9

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107.

CBO. The 2024 Long-Term Budget Outlook. https://www.cbo.gov/publication/60039 (2024).

108.

World Bank, B. of E. A. US GDP 2024 ($28.78 trillion). World Bank https://data.worldbank.org/indicator/NY.GDP.MKTP.CD?locations=US (2024)

US GDP reached $28.78 trillion in 2024, representing approximately 26% of global GDP. Additional sources: https://data.worldbank.org/indicator/NY.GDP.MKTP.CD?locations=US | https://www.bea.gov/news/2024/gross-domestic-product-fourth-quarter-and-year-2024-advance-estimate

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109.

Group, E. W. US farm subsidy database and analysis. Environmental Working Group https://farm.ewg.org/ (2024)

US agricultural subsidies total approximately $30 billion annually, but create much larger economic distortions. Top 10% of farms receive 78% of subsidies, benefits concentrated in commodity crops (corn, soy, wheat, cotton), environmental damage from monoculture incentivized, and overall deadweight loss estimated at $50-120 billion annually. Additional sources: https://farm.ewg.org/ | https://www.ers.usda.gov/topics/farm-economy/farm-sector-income-finances/government-payments-the-safety-net/

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110.

Alliance, D. P. The drug war by the numbers. (2021)

Since 1971, the war on drugs has cost the United States an estimated $1 trillion in enforcement. The federal drug control budget was $41 billion in 2022. Mass incarceration costs the U.S. at least $182 billion every year, with over $450 billion spent to incarcerate individuals on drug charges in federal prisons.

111.

Fund, I. M. IMF fossil fuel subsidies data: 2023 update. (2023)

Globally, fossil fuel subsidies were $7 trillion in 2022 or 7.1 percent of GDP. The United States subsidies totaled $649 billion. Underpricing for local air pollution costs and climate damages are the largest contributor, accounting for about 30 percent each.

112.

Papanicolas, I. et al. Health care spending in the united states and other high-income countries. Papanicolas et al. https://jamanetwork.com/journals/jama/article-abstract/2674671 (2018)

The US spent approximately twice as much as other high-income countries on medical care (mean per capita: $9,892 vs $5,289), with similar utilization but much higher prices. Administrative costs accounted for 8% of US spending vs 1-3% in other countries. US spending on pharmaceuticals was $1,443 per capita vs $749 elsewhere. Despite spending more, US health outcomes are not better. Additional sources: https://jamanetwork.com/journals/jama/article-abstract/2674671

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113.

Hsieh, C.-T. & Moretti, E. Housing constraints and spatial misallocation. American Economic Journal: Macroeconomics https://www.aeaweb.org/articles?id=10.1257/mac.20170388 (2019)

We quantify the amount of spatial misallocation of labor across US cities and its aggregate costs. Tight land-use restrictions in high-productivity cities like New York, San Francisco, and Boston lowered aggregate US growth by 36% from 1964 to 2009. Local constraints on housing supply have had enormous effects on the national economy. Additional sources: https://www.aeaweb.org/articles?id=10.1257/mac.20170388

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114.

Lab, Y. B. The fiscal, economic, and distributional effects of all u.s. tariffs. (2025)

Accounting for all the 2025 US tariffs and retaliation implemented to date, the level of real GDP is persistently -0.6% smaller in the long run, the equivalent of $160 billion 2024$ annually.

115.

Foundation, T. Tax compliance costs the US economy $546 billion annually. https://taxfoundation.org/data/all/federal/irs-tax-compliance-costs/ (2024)

Americans will spend over 7.9 billion hours complying with IRS tax filing and reporting requirements in 2024. This costs the economy roughly $413 billion in lost productivity. In addition, the IRS estimates that Americans spend roughly $133 billion annually in out-of-pocket costs, bringing the total compliance costs to $546 billion, or nearly 2 percent of GDP.

116.

Cook, C., Cole, G., Asaria, P., Jabbour, R. & Francis, D. P. Annual global economic burden of heart disease. International Journal of Cardiology https://www.internationaljournalofcardiology.com/article/S0167-5273(13)02238-9/abstract (2014)

Heart failure alone: $108 billion/year (2012 global analysis, 197 countries) US CVD: $555B (2016) → projected $1.8T by 2050 LMICs total CVD loss: $3.7T cumulative (2011-2015, 5-year period) CVD is costliest disease category in most developed nations Note: No single $2.1T global figure found; estimates vary widely by scope and year Additional sources: https://www.ahajournals.org/doi/10.1161/CIR.0000000000001258

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117.

Source: US Life Expectancy FDA Budget 1543-2019 CSV. US life expectancy growth 1880-1960: 3.82 years per decade. (2019)

Pre-1962: 3.82 years/decade Post-1962: 1.54 years/decade Reduction: 60% decline in life expectancy growth rate Additional sources: https://ourworldindata.org/life-expectancy | https://www.mortality.org/ | https://www.cdc.gov/nchs/nvss/mortality_tables.htm

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118.

Source: US Life Expectancy FDA Budget 1543-2019 CSV. Post-1962 slowdown in life expectancy gains. (2019)

Pre-1962 (1880-1960): 3.82 years/decade Post-1962 (1962-2019): 1.54 years/decade Reduction: 60% decline Temporal correlation: Slowdown occurred immediately after 1962 Kefauver-Harris Amendment Additional sources: https://ourworldindata.org/life-expectancy | https://www.mortality.org/ | https://www.cdc.gov/nchs/nvss/mortality_tables.htm

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119.

Centers for Disease Control and Prevention. US life expectancy 2023. (2024)

US life expectancy at birth was 77.5 years in 2023 Male life expectancy: 74.8 years Female life expectancy: 80.2 years This is 6-7 years lower than peer developed nations despite higher healthcare spending Additional sources: https://www.cdc.gov/nchs/fastats/life-expectancy.htm

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120.

Bureau, U. C. US median household income 2023. (2024)

US median household income was $77,500 in 2023 Real median household income declined 0.8% from 2022 Gini index: 0.467 (income inequality measure) Additional sources: https://www.census.gov/library/publications/2024/demo/p60-282.html

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121.

Statista. US military budget as percentage of GDP. Statista https://www.statista.com/statistics/262742/countries-with-the-highest-military-spending/ (2024)

U.S. military spending amounted to 3.5% of GDP in 2024. In 2024, the U.S. spent nearly $1 trillion on its military budget, equal to 3.4% of GDP. Additional sources: https://www.statista.com/statistics/262742/countries-with-the-highest-military-spending/ | https://www.sipri.org/sites/default/files/2025-04/2504_fs_milex_2024.pdf

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122.

Bureau, U. C. Number of registered or eligible voters in the u.s. US Census Bureau https://www.census.gov/newsroom/press-releases/2025/2024-presidential-election-voting-registration-tables.html (2024)

73.6% (or 174 million people) of the citizen voting-age population was registered to vote in 2024 (Census Bureau). More than 211 million citizens were active registered voters (86.6% of citizen voting age population) according to the Election Assistance Commission. Additional sources: https://www.census.gov/newsroom/press-releases/2025/2024-presidential-election-voting-registration-tables.html | https://www.eac.gov/news/2025/06/30/us-election-assistance-commission-releases-2024-election-administration-and-voting

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123.

Senate, U. S. Treaties. U.S. Senate https://www.senate.gov/about/powers-procedures/treaties.htm

The Constitution provides that the president ’shall have Power, by and with the Advice and Consent of the Senate, to make Treaties, provided two-thirds of the Senators present concur’ (Article II, section 2). Treaties are formal agreements with foreign nations that require two-thirds Senate approval. 67 senators (two-thirds of 100) must vote to ratify a treaty for it to take effect. Additional sources: https://www.senate.gov/about/powers-procedures/treaties.htm

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124.

Commission, F. E. Statistical summary of 24-month campaign activity of the 2023-2024 election cycle. (2023)

Presidential candidates raised $2 billion; House and Senate candidates raised $3.8 billion and spent $3.7 billion; PACs raised $15.7 billion and spent $15.5 billion. Total federal campaign spending approximately $20 billion. Additional sources: https://www.fec.gov/updates/statistical-summary-of-24-month-campaign-activity-of-the-2023-2024-election-cycle/

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125.

OpenSecrets. Federal lobbying hit record $4.4 billion in 2024. (2024)

Total federal lobbying reached record $4.4 billion in 2024. The $150 million increase in lobbying continues an upward trend that began in 2016. Additional sources: https://www.opensecrets.org/news/2025/02/federal-lobbying-set-new-record-in-2024/

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126.

Hutchinson & Kirk. Valley of death in drug development. (2011)

The overall failure rate of drugs that passed into Phase 1 trials to final approval is 90%. This lack of translation from promising preclinical findings to success in human trials is known as the "valley of death." Estimated 30-50% of promising compounds never proceed to Phase 2/3 trials primarily due to funding barriers rather than scientific failure. The late-stage attrition rate for oncology drugs is as high as 70% in Phase II and 59% in Phase III trials.

127.

DOT. DOT value of statistical life ($13.6M). DOT: VSL Guidance 2024 https://www.transportation.gov/office-policy/transportation-policy/revised-departmental-guidance-on-valuation-of-a-statistical-life-in-economic-analysis (2024)

Current VSL (2024): $13.7 million (updated from $13.6M) Used in cost-benefit analyses for transportation regulations and infrastructure Methodology updated in 2013 guidance, adjusted annually for inflation and real income VSL represents aggregate willingness to pay for safety improvements that reduce fatalities by one Note: DOT has published VSL guidance periodically since 1993. Current $13.7M reflects 2024 inflation/income adjustments Additional sources: https://www.transportation.gov/office-policy/transportation-policy/revised-departmental-guidance-on-valuation-of-a-statistical-life-in-economic-analysis | https://www.transportation.gov/regulations/economic-values-used-in-analysis

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128.

ONE, P. Cost per DALY for vitamin a supplementation. PLOS ONE: Cost-effectiveness of "Golden Mustard" for Treating Vitamin A Deficiency in India (2010) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012046 (2010)

India: $23-$50 per DALY averted (least costly intervention, $1,000-$6,100 per death averted) Sub-Saharan Africa (2022): $220-$860 per DALY (Burkina Faso: $220, Kenya: $550, Nigeria: $860) WHO estimates for Africa: $40 per DALY for fortification, $255 for supplementation Uganda fortification: $18-$82 per DALY (oil: $18, sugar: $82) Note: Wide variation reflects differences in baseline VAD prevalence, coverage levels, and whether intervention is supplementation or fortification Additional sources: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012046 | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266495

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129.

News, U. Clean water & sanitation (LMICs) ROI. UN News https://news.un.org/en/story/2014/11/484032 (2014).

130.

PMC. Cost-effectiveness threshold ($50,000/QALY). PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC5193154/

The $50,000/QALY threshold is widely used in US health economics literature, originating from dialysis cost benchmarks in the 1980s. In US cost-utility analyses, 77.5% of authors use either $50,000 or $100,000 per QALY as reference points. Most successful health programs cost $3,000-10,000 per QALY. WHO-CHOICE uses GDP per capita multiples (1× GDP/capita = "very cost-effective", 3× GDP/capita = "cost-effective"), which for the US ( $70,000 GDP/capita) translates to $70,000-$210,000/QALY thresholds. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC5193154/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC9278384/

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131.

Institute, I. B. Chronic illness workforce productivity loss. Integrated Benefits Institute 2024 https://www.ibiweb.org/resources/chronic-conditions-in-the-us-workforce-prevalence-trends-and-productivity-impacts (2024)

78.4% of U.S. employees have at least one chronic condition (7% increase since 2021) 58% of employees report physical chronic health conditions 28% of all employees experience productivity loss due to chronic conditions Average productivity loss: $4,798 per employee per year Employees with 3+ chronic conditions miss 7.8 days annually vs 2.2 days for those without Note: 28% productivity loss translates to roughly 11 hours per week (28% of 40-hour workweek) Additional sources: https://www.ibiweb.org/resources/chronic-conditions-in-the-us-workforce-prevalence-trends-and-productivity-impacts | https://www.onemedical.com/mediacenter/study-finds-more-than-half-of-employees-are-living-with-chronic-conditions-including-1-in-3-gen-z-and-millennial-employees/ | https://debeaumont.org/news/2025/poll-the-toll-of-chronic-health-conditions-on-employees-and-workplaces/

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